@article{%a1.%Y_135,

title = {CRISPR/Cas9 mediated Y-chromosome elimination affects human cells transcriptome},

author = {Celli L and Gasparini P and Biino G and Zannini L and Cardano M},

url = {https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-024-01198-5},

doi = {10.1186/s13578-024-01198-5},

year  = {2024},

date = {2024-02-12},

journal = {Cell & bioscience},

volume = {14},

issue = {1},

pages = {15},

abstract = {Background: Sexual dimorphism represents a key concept in the comprehension of molecular processes guiding several sex-specific physiological and pathological mechanisms. It has been reported that genes involved in many disorders show a sex-dependent expression pattern. Moreover, the loss of Y chromosome (LOY), found to be a physiological age-driven phenomenon, has been linked to many neurodegenerative and autoimmune disorders, and to an increased cancer risk. These findings drove us towards the consideration that LOY may cause the de-regulation of disease specific networks, involving genes located in both autosomal and sex chromosomes. Results: Exploiting the CRISPR/Cas9 and RNA-sequencing technologies, we generated a Y-deficient human cell line that has been investigated for its gene expression profile. Our results showed that LOY can influence the transcriptome displaying relevant enriched biological processes, such as cell migration regulation, angiogenesis and immune response. Interestingly, the ovarian follicle development pathway was found enriched, supporting the female-mimicking profile of male Y-depleted cells. Conclusion: This study, besides proposing a novel approach to investigate sex-biased physiological and pathological conditions, highlights new roles for the Y chromosome in the sexual dimorphism characterizing human health and diseases. Moreover, this analysis paves the way for the research of new therapeutic approaches for sex dimorphic and LOY-related diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_74,

title = {Rare variant analyses across multiethnic cohorts identify novel genes for refractive error},

author = {Musolf AM and Haarman AEG and Luben RN and Ong JS and Patasova K and Trapero RH and Marsh J and Jain I and Jain R and Wang PZ and Lewis DD and Tedja MS and Iglesias AI and Li H and Cowan CS and {Consortium for Refractive Error and Myopia (CREAM)} and Biino G and Klein AP and Duggal P and Mackey DA and Hayward C and Haller T and Metspalu A and Wedenoja J and Parssinen O and Cheng CY and Saw SM and Stambolian D and Hysi PG and Khawaja AP and Vitart V and Hammond CJ and {van Duijn CM} and Verhoeven VJM and Klaver CCW and Bailey-Wilson JE.},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810640/},

doi = {10.1038/s42003-022-04323-7},

year  = {2023},

date = {2023-03-16},

journal = {Communications biology},

volume = {6},

issue = {1},

pages = {6},

abstract = {Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb__109,

title = {The Effect of Crackers Enriched with Camelina Sativa Oil on Omega-3 Serum Fatty Acid Composition in Older Adults: A Randomized Placebo-Controlled Pilot Trial},

author = {De Giuseppe R and Di Napoli I and Tomasinelli CE and Vincenti A and Biino G and Sommella E and Ferron L and Campiglia P and Ferrara F and Casali PM and Cena H



},

url = {https://link.springer.com/article/10.1007/s12603-023-1925-x},

doi = {10.1007/s12603-023-1925-x},

year  = {2023},

date = {2023-08-08},

journal = {Journal of nutrition health & aging},

volume = {27},

number = {463-471},

issue = {6},

abstract = {Background: Camelina sativa oil is one of the richest dietary sources of omega-3, with polyunsaturated fatty acids amounts of over 50%, linolenic acid content of around 40-45%, and linoleic acid of about 15%. Moreover, this oil is a valuable source of antioxidants which provide oxidative stability. All those features raise interest in considering Camelina oil as an alternative and sustainable oil source providing stable omega-3-rich emulsions for functional food production. Objectives: The present study aimed to investigate the effects of Camelina oil-enriched crackers on serum omega-3 concentration, inflammatory markers and serum lipid profile. Design: Randomized placebo-controlled pilot trial. Setting: Research and Development Center (Complife Italia s.r.l.). Participants: Sixty-six free-living older volunteers (aged≥65 years). Intervention: Older adults were enrolled and randomly assigned to one of two groups: the camelina group or the placebo group. Subjects consumed daily 35 g of crackers (Camelina enriched crackers or placebo ones) twice daily for 12 weeks. Measurements: Serum polyunsaturated fatty acid profile, inflammatory status and serum lipid panel parameters were recorded pre and post-intervention. Results: In the camelina group, alpha-linolenic acid serum concentration was significantly higher (p<0.01) compared to the placebo group at the end of the study. Concerning inflammatory plasma markers, a significant mean pro-inflammatory interleukin-18 plasma concentration decrease in the placebo group compared to the camelina one was observed (p<0.05). No significant differences in other mean inflammatory markers concentrations post-intervention were noted in either group. Lastly, examining the change in lipid profile, it is noteworthy that a higher reduction of total cholesterol, low-density lipoprotein and triglycerides in the camelina group post-intervention, despite the lack of statistical significance. Conclusion: Camelina oil significantly elevated the serum alpha-linolenic acid concentration with no significant changes in inflammatory markers and lipid profile. Trial registration: ClinicalTrials.gov NCT04965948.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_35,

title = {A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids},

author = {Ramdas S and Judd J and {………} and Biino G and {……..} and {et al.}},

url = {https://www.sciencedirect.com/science/article/pii/S0002929722002658?via%3Dihub},

doi = {10.1016/j.ajhg.2022.06.012},

year  = {2022},

date = {2022-08-18},

journal = {American journal of human genetics},

volume = {109},

issue = {8},

pages = {1366-1387},

abstract = {A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_66,

title = {A saturated map of common genetic variants associated with human height},

author = {Yengo L and Vedantam S and Marouli E and Sidorenko J and Bartell E and Sakaue S and Graff M and Eliasen AU and Jiang Y and Raghavan S and Miao J and Arias JD and Graham SE and Mukamel RE and Spracklen CN and Yin X and Chen SH and Ferreira T and Highland HH and Ji Y and Karaderi T and Lin K and Lüll K and Malden DE and Medina-Gomez C and Machado and ……. and Biino G and ….. and {et al}},

url = {https://www.nature.com/articles/s41586-022-05275-y},

doi = {10.1038/s41586-022-05275-y.},

year  = {2022},

date = {2022-03-24},

journal = {Nature},

volume = {610},

issue = {7933},

pages = {704-712},

abstract = {Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yby,

title = {Development of a Short Questionnaire for the Screening for Vitamin D Deficiency in Italian Adults: The EVIDENCe-Q Project},

author = {{De Giuseppe R} and Tomasinelli CE and Cena H and Braschi V and Giampieri F and Preatoni G and Centofanti D and Princis MP and Bartoletti E and Biino G},

url = {https://www.mdpi.com/2072-6643/14/9/1772},

doi = {10.3390/nu14091772},

year  = {2022},

date = {2022-08-23},

journal = {Nutrients},

volume = {14},

issue = {9},

pages = {1772},

abstract = {Background: To develop and validate a questionnaire for the screening of Vitamin D in Italian adults (Evaluation Vitamin D dEficieNCy Questionnaire, EVIDENCe-Q). Methods: 150 participants, attending the 11Clinical Nutrition and Dietetics Operative Unit, Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, of Pavia were enrolled. Demographic variables and serum levels of vitamin D were recorded. The EVIDENCe-Q included information regarding factors affecting the production, intake, absorption and metabolism of Vitamin D. The EVIDENCe-Q score ranged from 0 (the best status) to 36 (the worst status). Results: Participants showed an inadequate status of Vitamin D, according to the current Italian reference values. A significant difference (p < 0.0001) in the EVIDENCe-Q score was found among the three classes of vitamin D status (severe deficiency, deficiency and adequate), being the mean score higher in severe deficiency and lower in the adequate one. A threshold value for EVIDENCe-Q score of 23 for severe deficiency, a threshold value of 21 for deficiency and a threshold value of 20 for insufficiency were identified. According to these thresholds, the prevalence of severe deficiency, deficiency and insufficiency was 22%, 35.3% and 43.3% of the study population, respectively. Finally, participants with EVIDENCe-Q scores <20 had adequate levels of vitamin D. Conclusions: EVIDENCe-Q can be a useful and easy screening tool for clinicians in their daily practice at a reasonable cost, to identify subjects potentially at risk of vitamin D deficiency and to avoid unwarranted supplementation and/or costly blood testing},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_67,

title = {Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals},

author = {Winkler TW and Rasheed H and Teumer A and Gorski M and Rowan BX and Stanzick KJ and Thomas LF and Tin A and Hoppmann A and Chu AY and Tayo B and Thio CHL and Cusi D and Chai JF and Sieber KB and Horn K and Li M and Scholz M and Cocca M and Wuttke M and van der Most PJ and Yang Q and Ghasemi S and Nutile T and Li Y and ……. and Biino G and ……. {et al}},

url = {https://www.nature.com/articles/s42003-022-03448-z},

doi = {Communications biology},

year  = {2022},

date = {2022-03-26},

journal = {Communications biology},

volume = {5},

issue = {1},

pages = {580},

abstract = {Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_28,

title = {Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies},

author = {Gorski M and Rasheed H and Teumer A and Thomas LF and Graham SE and Sveinbjornsson G and Winkler TW and Gunther F and Stark KJ and Chai JF and Tayo BO and Wuttke M and Li Y and Tin A and Ahluwalia TS and Ärnlöv J and Åsvold BO and Bakker SJL and Banas B and Bansal N and Biggs ML and Biino G and {et al}},

url = {https://www.sciencedirect.com/science/article/pii/S0085253822004549?via%3Dihub},

doi = {10.1016/j.kint.2022.05.021},

year  = {2022},

date = {2022-08-25},

journal = {Kidney international},

volume = {102},

issue = {3},

pages = {624-639},

abstract = {Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_53,

title = {Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis},

author = {Kanoni S and Graham SE and Wang Y and Surakka I and …. and Biino G and ….. and Deloukas P and Willer CJ and Assimes TL and Peloso GM},

url = {https://genomebiology.biomedcentral.com/articles/10.1186/s13059-022-02837-1},

doi = {10.1186/s13059-022-02837-1},

year  = {2022},

date = {2022-03-30},

urldate = {2022-03-30},

journal = {Genome biology},

volume = {23},

issue = {1},

pages = {268},

abstract = {Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_60,

title = {Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals.},

author = {Okbay A and Wu Y and Wang N and Jayashankar H and Bennett M and Nehzati SM and …... and Biino G and …..... and et al},

url = {https://www.nature.com/articles/s41588-022-01016-z},

doi = {10.1038/s41588-022-01016-z},

year  = {2022},

date = {2022-03-31},

journal = {Nature genetics},

volume = {54},

issue = {4},

pages = {437-449},

abstract = {We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of  about 3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_43,

title = {Screening Questionnaire for Vitamin D Insufficiency in Children with Obesity},

author = {Calcaterra V and Cena H and Biino G and Grazi R and Bortoni G and Braschi V and Tomasinelli CE and Schneider L and Zuccotti G},

url = {https://www.mdpi.com/2227-9067/9/11/1685},

doi = {https://www.mdpi.com/2227-9067/9/11/1685},

year  = {2022},

date = {2022-03-25},

urldate = {2022-03-25},

journal = {Children (Basel)},

volume = {9},

issue = {11},

pages = {1685},

abstract = {"Non-invasive screening tools to identify children at high risk of vitamin D (VitD) deficiency are proactive measures in preventive care. Recently, a validated questionnaire (Evaluation dEficieNCy Questionnaire, EVIDENCe-Q) for identifying newly diagnosed VitD-insufficient adults has been developed. We tested the EVIDENCe-Q modified for children with obesity and evaluated the correlation between VitD and questionnaire scores to adapt this tool to the pediatric population. We enrolled 120 children with obesity (BMI ≥ 2). Clinical evaluation and VitD levels were considered. The modified EVIDENCe-Q included information regarding factors affecting control of VitD, with scores ranging between 0 (best) and 36 (worst). VitD and adiposity indices were inversely correlated. The threshold values for identifying severe deficiency (<10 mg/dL), deficiency (<20 mg/dL) and insufficiency (<30 mg/dL) were scores of 21, 19 and 23, respectively. According to those thresholds, the prevalence of severe deficiency, deficiency and insufficiency was 47.5%, 69.2% and 23.3%, respectively; the best accuracy was obtained with a questionnaire score cut-off of 19 for the VitD deficiency level. A novel simple screening tool such as the modified EVIDENCe-Q would be useful in clinical practice to identify potential cases of hypovitaminosis D and select at-risk patients. Considering the limited accuracy and specificity of our results, for the pediatric population a dedicated tool should be created. Phases of childhood and the role of adipose tissue could be considered in the definition of a questionnaire intended for pediatric patients with obesity.

"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__516,

title = {Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia},

author = {Tideman JWL and Parssinen O and Haarman AEG and Khawaja AP and Wedenoja J and Williams KM and Biino G and Ding X and Kahonen M and Lehtimaki T and Raitakari OT and Cheng CY and Jonas JB and Young TL and Bailey-Wilson JE and Rahi J and Williams C and He M and Mackey DA and Guggenheim JA and {UK Biobank Eye and Vision Consortium} and {the Consortium for Refractive Error and Myopia} (CREAM Consortium)},

url = {https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2778382},

doi = {10.1001/jamaophthalmol.2021.0497},

year  = {2021},

date = {2021-09-13},

urldate = {2021-04-14},

journal = {JAMA ophthalmology},

volume = {139},

number = {6},

pages = {601-609},

abstract = {Importance: Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. Objective: To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. Design, setting, and participants: This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020. Exposures: Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry. Main outcomes and measures: Odds ratios (ORs) of polygenic risk scores in replication samples. Results: A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16). Conclusions and relevance: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__514,

title = {Lifestyle Changes and Body Mass Index during COVID-19 Pandemic Lockdown: An Italian Online-Survey},

author = {Maffoni S and Brazzo S and De Giuseppe R and Biino G and Vietti I and Pallavicini C and Cena H},

url = {https://www.mdpi.com/2072-6643/13/4/1117},

doi = {https://www.mdpi.com/2072-6643/13/4/1117},

year  = {2021},

date = {2021-04-14},

journal = {Nutrients},

volume = {13},

number = {4},

pages = {1117},

abstract = {Background: COVID-19 pandemic has imposed a period of contingency measures, including total or partial lockdowns all over the world leading to several changes in lifestyle/eating behaviours. This retrospective cohort study aimed at investigating Italian adult population lifestyle changes during COVID-19 pandemic "Phase 1" lockdown (8 March-4 May 2020) and discriminate between positive and negative changes and BMI (body mass index) variations (ΔBMI). Methods: A multiple-choice web-form survey was used to collect retrospective data regarding lifestyle/eating behaviours during "Phase 1" in the Italian adult population. According to changes in lifestyle/eating behaviours, the sample was divided into three classes of changes: "negative change", "no change", "positive change". For each class, correlations with ΔBMI were investigated. Results: Data were collected from 1304 subjects (973F/331M). Mean ΔBMI differed significantly (p < 0.001) between classes, and was significantly related to water intake, alcohol consumption, physical activity, frequency of ""craving or snacking between meals"", dessert/sweets consumption at lunch. Conclusions: During "Phase 1", many people faced several negative changes in lifestyle/eating behaviours with potential negative impact on health. These findings highlight that pandemic exacerbates nutritional issues and most efforts need to be done to provide nutrition counselling and public health services to support general population needs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Yb_64,

title = {The power of genetic diversity in genome-wide association studies of lipids.},

author = {Graham SE and Clarke SL and Wu KH and Kanoni S and Zajac GJM ...... and Biino G and et al.},

url = {https://www.nature.com/articles/s41586-021-04064-3},

doi = {10.1038/s41586-021-04064-3},

year  = {2021},

date = {2021-12-14},

urldate = {2021-12-14},

journal = {Nature},

volume = {600},

number = {7890},

pages = {675-679},

abstract = {Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_450,

title = {Genome-wide Association Meta-Analysis of Corneal Curvature Identifies Novel Loci and Shared Genetic Influences Across Axial Length and Refractive Error},

author = {Fan Q and Pozarickij A and Tan NYQ and Guo X and Verhoeven VJM and Vitart V and Guggenheim JA and Miyake M and Tideman JWL and Khawaja AP and Zhang L and MacGregor S and Hohn R and Chen P and Biino G and and Wedenoja J al.},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081241/},

doi = {10.1038/s42003-020-0802-y},

year  = {2020},

date = {2020-01-01},

journal = {Communications biology},

volume = {3},

number = {1},

pages = {133},

abstract = {Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_479,

title = {The association between weight-promoting medication use and weight gain in postmenopausal women: findings from the Women's Health Initiative},

author = {Stanford FC and Cena H and Biino G and Umoren O and Jimenez M and Freeman MP and Shadyab AH and Wild RA and Womack CR and Banack HR and Manson JE},

doi = {10.1097/GME.0000000000001589},

year  = {2020},

date = {2020-01-01},

journal = {Menopause (N. Y. N. Y., Online)},

volume = {27},

number = {10},

pages = {1117-1125},

abstract = {Objective: With the rise in obesity, there has been a concomitant increase in prescription medications associated with weight gain. The objective of this study is to quantify the magnitude of association between putative weight-promoting medications and 3-year weight change in a diverse cohort of postmenopausal women in the Women's Health Initiative (WHI).  Methods: This is a prospective observational cohort study, considering 40 sites in the WHI and a cohort of seventy six thousand two hundred fifty-two postmenopausal women aged 50-79 years, with weight measured at both baseline and 3 years, in the WHI-Observational Study. Body mass index (BMI) and waist circumference (WC) were measured at baseline and 3 years. An in-clinic medication inventory identified prescribed medications, including antidepressants, beta-blockers, insulin, and/or glucocorticosteroids. Generalized linear models evaluated if intermittent or persistent use of weight-promoting drugs was associated with increased BMI and WC during a 3-year follow up. Results: Women with overweight or obesity at baseline were more likely to be taking antidepressants, beta-blockers, and/or insulin. Taking at least one putative weight-promoting medication was associated with a greater increase in BMI (0.37 vs 0.27 kg/m, P = 0.0045) and WC (1.10 cm vs 0.89 cm, P = 0.0077) over the course of 3 years compared to women not on these medications. Both BMI and WC increased with the number of weight-promoting drugs prescribed (P for trend per medication used < 0.00001 for both variables). Those who took either antidepressants or insulin, or a combination of antidepressants and beta-blockers, were most likely to have a significant increase in BMI compared to nonusers. Conclusions: Antidepressants, beta-blockers, and insulin were associated with weight gain in postmenopausal women. This information may help to inform clinical decision-making and efforts to mitigate medication-related weight gain. : Video Summary:http://links.lww.com/MENO/A617.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_443,

title = {Unhealthy Lifestyle and Oxidative Damage in Childhood Obesity},

author = {{De Giuseppe R} and Calcaterra V and Biino G and Manuelli M and Mier NR and Mantelli M and {De Filippo M} and Cossellu G and Cena H},

url = {https://link.springer.com/article/10.1007%2Fs40519-018-0626-7},

doi = {10.1007/s40519-018-0626-7},

year  = {2020},

date = {2020-01-01},

journal = {Eating and weight disorders : EWD.},

volume = {25},

number = {2},

pages = {481-486},

abstract = {Purpose: Oxidized LDL cholesterol (oxLDL) has been considered as a sensor of oxidative stress (OS) in childhood obesity. We integrated and related our oxLDL existing results previously assessed in overweight/obese children to lifestyle variables to investigate OS-related lifestyle variables. Methods: 178 Caucasian children/adolescents have been evaluated and according to BMI percentiles have been classified as normal weight (BMI < 75th); overweight (BMI 75-97th) and obese (BMI > 97th). Serum oxLDL levels have been measured. The dietary habits and physical activity have been also assessed. Results: No differences between normal weight and overweight/obese children were detected according to the total score of dietary habits section. Normal weight subjects reported a higher total physical activity score (p = 0.001) compared to overweight/ obese children. No correlation between oxLDL and total dietary habits and physical activity scores was noted. Increased oxLDL in subjects drinking < 1 L/day of water (p = 0.022) and in daily consumers of chocolate drinks at breakfast (p = 0.029) was observed, while a decreased oxLDL was reported in subjects consuming a breakfast based mainly on fruits (p = 0.004). Moreover, "high-fat diet" and "always eating a dessert at the end of the meal" were correlated with increased oxLDL with a trend towards significance. As regards physical activity, no correlations were observed. Conclusions: Diet and physical activity may not have an immediate impact on OS response in children with or without obesity. Unhealthy lifestyle, including increased fat, simple sugar intake, poor water intake, emerged as external exposome predictors of OS, that may be monitored to improve health status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_322,

title = {Unhealthy lifestyle and oxidative damage in childhood obesity.},

author = {{De Giuseppe R} and Calcaterra V and Biino G and Manuelli M and Mier NR and Mantelli M and De Filippo M and Cossellu G and Cena H},

url = {https://link.springer.com/article/10.1007%2Fs40519-018-0626-7#citeas},

doi = {10.1007/s40519-018-0626-7},

year  = {2020},

date = {2020-03-03},

journal = {Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity},

abstract = {PURPOSE: Oxidized LDL cholesterol (oxLDL) has been considered as a sensor of oxidative stress (OS) in childhood obesity. We integrated and related our oxLDL existing results previously assessed in overweight/obese children to lifestyle variables to investigate OS-related lifestyle variables. METHODS: 178 Caucasian children/adolescents have been evaluated and according to BMI percentiles have been classified as normal weight (BMI < 75th); overweight (BMI 75-97th) and obese (BMI > 97th). Serum oxLDL levels have been measured. The dietary habits and physical activity have been also assessed. RESULTS: No differences between normal weight and overweight/obese children were detected according to the total score of dietary habits section. Normal weight subjects reported a higher total physical activity score (p = 0.001) compared to overweight/ obese children. No correlation between oxLDL and total dietary habits and physical activity scores was noted. Increased oxLDL in subjects drinking < 1 L/day of water (p = 0.022) and in daily consumers of chocolate drinks at breakfast (p = 0.029) was observed, while a decreased oxLDL was reported in subjects consuming a breakfast based mainly on fruits (p = 0.004). Moreover, "high-fat diet" and "always eating a dessert at the end of the meal" were correlated with increased oxLDL with a trend towards significance. As regards physical activity, no correlations were observed. CONCLUSIONS: Diet and physical activity may not have an immediate impact on OS response in children with or without obesity. Unhealthy lifestyle, including increased fat, simple sugar intake, poor water intake, emerged as external exposome predictors of OS, that may be monitored to improve health status. LEVEL OF EVIDENCE: Level III, case-control analytic studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_45,

title = {A catalog of genetic loci associated with kidney function from analyses of a million individuals.},

author = {Wuttke M and Li Y and Li M and Sieber KB and Feitosa MF and Gorski M and Tin A and Wang L and Chu AY and Hoppmann A and Kirsten H and Giri A and Chai JF and Sveinbjornsson G and Tayo BO and Nutile T and Fuchsberger C and Marten J and Cocca M and Ghasemi S and Xu Y and Horn K and Noce D and van der Most PJ and Sedaghat S and Yu Z and Akiyama M and Afaq S and Ahluwalia TS and Almgren P and Amin N and Arnlov J and Bakker SJL and Bansal N and Baptista D and Bergmann S and Biggs ML and Biino G and {et al}},

url = {https://www.nature.com/articles/s41588-019-0407-x},

doi = {10.1038/s41588-019-0407-x},

year  = {2019},

date = {2019-02-15},

journal = {Nature Genetics},

volume = {51},

number = {6},

pages = {957-972},

abstract = {Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%x,

title = {Associations of autozygosity with a broad range of human phenotypes.},

author = {Clark DW and Okada Y and Moore KHS and Mason D and Pirastu N and Gandin I and Mattsson H and Barnes CLK and Lin K and Zhao JH and Deelen P and Rohde R and Schurmann C and Guo X and Giulianini F and Zhang W and Medina-Gomez C and Karlsson R and Bao Y and Bartz TM and Baumbach C and Biino G and {et al}},

url = {https://www.nature.com/articles/s41467-019-12283-6},

doi = {10.1038/s41467-019-12283-6},

year  = {2019},

date = {2019-02-15},

journal = {Nature Communications},

volume = {10},

number = {4957},

abstract = {In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_50,

title = {Body composition and resting energy expenditure in women with anorexia nervosa: Is hyperactivity a protecting factor?},

author = {Manuelli M and Blundell JE and Biino G and Cena H},

url = {https://www.sciencedirect.com/science/article/pii/S2405457718305473?via%3Dihub},

doi = {10.1016/j.clnesp.2018.10.015},

year  = {2019},

date = {2019-02-15},

journal = {Clinical Nutrition ESPEN},

volume = {29},

pages = {160-164},

abstract = {BACKGROUND: In subjects with anorexia nervosa (AN) physical exercise may cause or even prevent weight loss, body composition alterations and adaptive thermogenesis. To investigate the influence of behavioral patterns on body composition and energy expenditure in women with AN, we conducted a retrospective analysis in 62 patients with AN referring to our outpatients' clinic. MATERIALS AND METHODS: We assessed anthropometric measurement of weight, height, and BMI; body composition was assessed by bioelectrical impedance analysis; resting energy expenditure was measured through indirect calorimetry. Patients' characteristics were assessed at the time of first evaluation. RESULTS: The subjects were both restricting type (ANR, n = 39) and binge-eating/purging type (ANBP, n = 23) according to DSM-5. We observed a lower reactance (58.63 (11.9) vs. 66.5 (15.5) Ohm, p < 0.05) and higher total body water in ANR subjects. No differences were found in phase angle, fat mass or fat-free mass, nor in REE measures. Within ANR subgroup, we identified two behavioral patterns, with or without physical hyperactivity. Compared to dieting and fasting subjects, hyperactive subjects showed higher phase angle [5.6 (0.7) vs. 4.8 (0.8), p < 0.05], lower fat-free mass [82.5 (6.8) vs. 89.9 (7.5)%, p < 0.05], greater proportion of fat mass [17.5 (6.8) vs. 10.1 (7.5)%, p < 0.05] and body cell mass [46.6 (5.1) vs. 42.5 (5.5)%, p < 0.05]. Finally, hyperactive subjects had greater BMI than dieting or fasting subjects [18.2 (1.7) vs. 15.8 (1.7), p < 0.005]. CONCLUSION: With limitations due to the small sample size, hyperactive subjects show body composition and energy metabolism features that seem protective in terms of prognosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_26,

title = {Dietary underreporting in women affected by polycystic ovary syndrome: A pilot study.},

author = {De Giuseppe R and Braschi V and Bosoni D and Biino G and Stanford FC and Nappi RE and Cena H},

doi = {10.1111/1747-0080.12460},

year  = {2019},

date = {2019-02-07},

journal = {Nutrition & dietetics},

volume = {76},

number = {5},

pages = {560-566},

abstract = {AIM: The first-line therapy for polycystic ovary syndrome (PCOS) is weight loss focussing on diet and regular exercise; measurement of diet and energy intake (EI) is important to determine associations between nutrients and health in women with PCOS. The EI underreporting (UR) is a condition characterised by reports of habitual EI that is implausibly low, compared with estimated requirements. This case-control study aims to evaluate UR in women with PCOS. METHODS: Thirty-six women with PCOS were enrolled according to the Rotterdam criteria; 37 healthy women were enrolled as controls. INCLUSION CRITERIA: age range 18-45 and body mass index ≥18.5 kg/m2 in subjects without eating disorders and/or diabetes mellitus. Nutritional assessment included: anthropometry, basal metabolic rate (BMR), weight history and physical activity assessment. Subjects completed a non-consecutive three-day dietary diary to identify energy and macronutrient intake. UR was calculated (Goldberg Index: EI/BMR). RESULTS: Although women with PCOS reported a significantly higher mean BMR than controls (P < 0.0001), their EI was lower (P < 0.001), suggesting an UR in 47.2% of women with PCOS versus 2.7% of controls (P < 0.0001). The EI from simple sugars was lower in women with PCOS than controls (P < 0.01). The protein intake was increased in controls than women with PCOS (P < 0.0001). Weight cycling was more frequent in women with PCOS (P < 0.001). Logistic regression analysis identified UR associated with PCOS (P = 0.001). CONCLUSIONS: Women with PCOS underreport foods rich in simple sugars rather than underreport their total dietary intake. These results may have implications for the interpretation of diet and health correlations in this patient population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_55,

title = {Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals.},

author = {Noordam R and Young WJ and Salman R and Kanters JK and van den Berg ME and van Heemst D and Lin HJ and Barreto SM and Biggs ML and Biino G and Catamo E and {et al}},

url = {https://www.sciencedirect.com/science/article/pii/S0735109719349939?via%3Dihub},

doi = {10.1016/j.jacc.2019.03.519},

year  = {2019},

date = {2019-02-14},

journal = {Journal of the American College of Cardiology},

volume = {73},

number = {24},

pages = {3118-3131},

abstract = {BACKGROUND: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions. OBJECTIVES: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population. METHODS: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs. RESULTS: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals. CONCLUSIONS: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms. Copyright 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_40,

title = {Estimation of metabolic syndrome heritability in three large populations including full pedigree and genomic information.},

author = {Graziano F and Biino G and Bonati MT and Neale BM and Do R and Concas MP and Vaccargiu S and Pirastu M and Terradura-Vagnarelli O and Cirillo M and Laurenzi M and Mancini M and Zanchetti A and Grassi M},

url = {https://link.springer.com/article/10.1007%2Fs00439-019-02024-6},

doi = {10.1007/s00439-019-02024-6},

year  = {2019},

date = {2019-07-13},

journal = {Human genetics},

volume = {138},

number = {7},

pages = {739-748},

abstract = {Metabolic syndrome is a complex human disorder characterized by a cluster of conditions (increased blood pressure, hyperglycemia, excessive body fat around the waist, and abnormal cholesterol or triglyceride levels). Any of these conditions increases the risk of serious disorders such as diabetes or cardiovascular disease. Currently, the degree of genetic regulation of this syndrome is under debate and partially unknown. The principal aim of this study was to estimate the genetic component and the common environmental effects in different populations using full pedigree and genomic information. We used three large populations (Gubbio, ARIC, and Ogliastra cohorts) to estimate the heritability of metabolic syndrome. Due to both pedigree and genotyped data, different approaches were applied to summarize relatedness conditions. Linear mixed models (LLM) using average information restricted maximum likelihood (AIREML) algorithm were applied to partition the variances and estimate heritability (h2) and common sib–household effect (c2). Globally, results obtained from pedigree information showed a significant heritability (h2: 0.286 and 0.271 in Gubbio and Ogliastra, respectively), whereas a lower, but still significant heritability was found using SNPs data (  h2SNP : 0.167 and 0.254 in ARIC and Ogliastra). The remaining heritability between h2 and  h2SNP  ranged between 0.031 and 0.237. Finally, the common environmental c2 in Gubbio and Ogliastra were also significant accounting for about 11% of the phenotypic variance. Availability of different kinds of populations and data helped us to better understand what happened when heritability of metabolic syndrome is estimated and account for different possible confounding. Furthermore, the opportunity of comparing different results provided more precise and less biased estimation of heritability.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%_44,

title = {Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences},

author = {Karlsson Linnér R and Biroli P and Kong E and {et al} and Biino G and {et al} },

url = {https://www.nature.com/articles/s41588-018-0309-3},

doi = {10.1038/s41588-018-0309-3 },

year  = {2019},

date = {2019-02-21},

journal = {Nature Genetics},

volume = {51},

number = {2},

pages = {245-257},

abstract = {Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (vertical bar(r) over cap (g)vertical bar similar to 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_76,

title = {Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.},

author = {Tin A and Marten J and Halperin Kuhns VL and Li Y and Wuttke M and Kirsten H and Sieber KB and Qiu C and Gorski M and Yu Z and Giri A and Sveinbjornsson G and Li M and Chu AY and Hoppmann A and O'Connor LJ and Prins B and Nutile T and Noce D and Akiyama M and Cocca M and Ghasemi S and van {der Most PJ} and Horn K and Xu Y and Fuchsberger C and Sedaghat S and Afaq S and Amin N and Arnlov J and Bakker SJL and Bansal N and Baptista D and Bergmann S and Biggs ML and Biino G and Boerwinkle E and {et al}},

url = {https://www.nature.com/articles/s41588-019-0504-x},

doi = {10.1038/s41588-019-0504-x},

year  = {2019},

date = {2019-10-31},

journal = {Nature genetics},

volume = {51},

number = {10},

pages = {1459-1474},

abstract = {Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_174,

title = {A genome-wide association study of corneal astigmatism: The CREAM Consortium.},

author = {Shah RL and Li Q and Zhao W and Tedja MS and Tideman JWL and Khawaja AP and Fan Q and Yazar S and Williams KM and Verhoeven VJM and Xie J and Wang YX and Hess M and Nickels S and Lackner KJ and Passinen O and Wedenoja J and Biino G and Concas MP and Uitterlinden A and Rivadeneira F and Jaddoe VWV and Hysi PG and Sim X and Tan N and Tham YC and Sensaki S and Hofman A and Vingerling JR and Jonas JB and Mitchell P and Hammond CJ and Höhn R and Baird PN and Wong TY and Cheng CY and Teo YY and Mackey DA and Williams C and Saw SM and Klaver CCW and Guggenheim JA and Bailey-Wilson JE and {CREAM Consortium}},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800430/},

doi = { 10.1177/0963689717725078},

year  = {2018},

date = {2018-02-22},

journal = {Molecular vision},

volume = {24},

pages = {127-142},

abstract = {PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_151,

title = {Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.},

author = {Lee JJ and Wedow R and Okbay A and et al and Biino G and et al},

url = {https://www.nature.com/articles/s41588-018-0147-3},

doi = {10.1038/s41588-018-0147-3},

year  = {2018},

date = {2018-07-23},

journal = {Nature Genetics},

volume = {50},

number = {8},

pages = {1112-1121},

abstract = {Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_152,

title = {Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.},

author = {Ligthart S and Vaez A and Vosa U and et al and Biino G and et al



},

url = {https://www.sciencedirect.com/science/article/pii/S0002929718303203?via%3Dihub},

doi = {10.1016/j.ajhg.2018.09.009},

year  = {2018},

date = {2018-02-16},

journal = {Annals of Human Genetics},

volume = {103},

number = {5},

pages = {691-706},

abstract = {C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_179,

title = {Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.},

author = {Tedja MS and Wojciechowski R and Hysi PG and Eriksson N and Furlotte NA and Verhoeven VJM and Iglesias AI and Meester-Smoor MA and Tompson SW and {et al} and Biino G and {et al} and Klaver CCW},

url = {https://www.nature.com/articles/s41588-018-0127-7},

doi = {10.1038/s41588-018-0127-7},

year  = {2018},

date = {2018-06-15},

journal = {Nature Genetics},

volume = {50},

number = {6},

pages = {834-848},

abstract = {Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_170,

title = {Technical and clinical feasibility of contrast-enhanced ultrasound evaluation of long bone non-infected nonunion healing.},

author = {Pozza S and De Marchi A and Albertin C and Albano D and Biino G and Aloj D and Sconfienza LM},

url = {https://link.springer.com/article/10.1007%2Fs11547-018-0902-7},

doi = {10.1007/s11547-018-0902-7},

year  = {2018},

date = {2018-09-21},

volume = {123},

number = {9},

pages = {703-709},

abstract = {PURPOSE: To assess the technical feasibility of contrast-enhanced ultrasound (CEUS) in the monitoring of non-infected long bone nonunion healing. METHODS: Twenty-five patients (16 males; mean age: 40.4 ± 11.7) with long bone nonunion were treated using surgery and mesenchymal stem cells and platelet-rich plasma. They performed CEUS up to 15 days before, 7 days, 4 and 8 weeks after treatment. To categorize the angiogenesis around the fracture site, the microvascular blood flow from CEUS was classified into four categories, depending on the portion of the investigated area that was involved in the neovascularization process: grade 0 = 0%; grade 1 = 0-30%; grade 2 = 30-70%; grade 3 = 70-100%. Nonparametric Friedman and Wilcoxon statistics were used. RESULTS: Before treatment, neovascularization was graded as 0 in 15/25 patients, as 1 in 10/25. Vascularity significantly increased over time (P < 0.001), namely: 1 (25th-75th percentile = 1-2) at 7 days; 2 (1-2) at 4 weeks; 3 (0-2) at 8 weeks. All patients but one showed early progressive increase in neovascularization well identified with CEUS at the fracture site. CONCLUSION: CEUS is a feasible method to monitor healing in patients with long bone nonunion.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_178,

title = {Weight Loss Medications in Older Adults After Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multicenter Study.},

author = {Stanford FC and Toth AT and Shukla AP and Pratt JS and Cena H and Biino G and Aronne LJ},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306651/},

doi = {10.1089/bari.2018.0037},

year  = {2018},

date = {2018-03-06},

journal = {Bariatric surgical practice and patient care},

volume = {13},

number = {4},

pages = {171-178},

abstract = {Weight loss medications are effective to confer additional weight loss after bariatric surgery in the general population, but they have not been evaluated in adults 60 years of age and older. We performed a retrospective study identifying 35 patients who were ≥60 years old and had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2000 to 2014, and were subsequently prescribed weight loss medications. Linear regression analyses were performed to determine beta coefficients of certain predictor variables being associated with weight loss. Patients lost weight on medications with an average body mass index (BMI) change of -2.74 kg/m2, standard deviation = 2.6 kg/m2. RYGB patients lost a greater percentage of BMI on medication than SG (SG; -1.38 +/- 1.49 kg/m2 and RYGB; -3.37 +/- 2.83 kg/m2, p = 0.0372). Patients with hypertension were less likely to lose weight on medications (β = 16.76, p = 0.004, and 95% confidence interval = 5.85-27.67). Weight loss medications are a useful treatment to confer additional weight loss in adults 60 years of age and older after RYGB and SG.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_180,

title = {Weight Loss Medications in Young Adults after Bariatric Surgery for Weight Regain or Inadequate Weight Loss: A Multi-Center Study.},

author = {Toth AT and Gomez G and Shukla AP and Pratt JS and Cena H and Biino G and Aronne LJ and Stanford FC},

url = {https://www.mdpi.com/2227-9067/5/9/116},

doi = {10.310.3390/children5090116390/children5090116},

year  = {2018},

date = {2018-03-07},

journal = {Children (Basel)},

volume = {5},

number = {9},

pages = {pii: E116},

abstract = {This paper presents a retrospective cohort study of weight loss medications in young adults aged 21 to 30 following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between November 2000 and June 2014. Data were collected from patients who used topiramate, phentermine, and/or metformin postoperatively. Percentage of patients achieving ≥5%, ≥10%, or ≥15% weight loss on medications was determined and percent weight change on each medication was compared to percent weight change of the rest of the cohort. Our results showed that 54.1% of study patients lost ≥5% of their postsurgical weight; 34.3% and 22.9% lost ≥10% and ≥15%, respectively. RYGB had higher median percent weight loss (-8.1%) than SG (-3.3%) (p = 0.0515). No difference was found in median percent weight loss with medications started at weight plateau (-6.0%) versus after weight regain (-5.4%) (p = 0.5304). Patients taking medications at weight loss plateau lost 41.2% of total body weight from before surgery versus 27.1% after weight regain (p = 0.076). Median percent weight change on metformin was -2.9% compared to the rest of the cohort at -7.7% (p = 0.0241). No difference from the rest of the cohort was found for phentermine (p = 0.2018) or topiramate (p = 0.3187). Topiramate, phentermine, and metformin are promising weight loss medications for 21 to 30 year olds. RYGB patients achieve more weight loss on medications but both RYGB and SG benefit. Median total body weight loss from pre-surgical weight may be higher in patients that start medication at postsurgical nadir weight. Participants on metformin lost significantly smaller percentages of weight on medications, which could be the result of underlying medical conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_237,

title = {Association of a history of childhood-onset obesity and dieting with eating disorders.},

author = {Cena H and Stanford FC and Ochner L and Fonte ML and Biino G and De Giuseppe R and Taveras E and Misra M},

url = {http://www.tandfonline.com/doi/abs/10.1080/10640266.2017.1279905?journalCode=uedi20},

doi = {10.1080/10640266.2017.1279905},

year  = {2017},

date = {2017-02-09},

journal = {Eating disorders },

volume = {25},

number = {3},

pages = {216-229},

abstract = {This was a retrospective, observational chart review conducted on a convenience sample of 537 outpatients, aged 16-60 years, referred to an Italian Dietetic and Nutrition University Center. The study aimed to look at the association between a history of childhood obesity and dieting behaviors with development of eating disorders (EDs) at a later age. Subjects with a history of EDs (n = 118), assessed using both self-report and health records, were compared with those with no EDs (n = 419), who were attending the clinic mainly for primary prevention of metabolic and cardiovascular risk. Logistic regression analysis was performed to assess the association of childhood-onset obesity with development of an ED at a later age. Childhood-onset obesity, gender, maternal history of eating disorders, and dieting were associated with a positive history of EDs at a later age (p < .05). It is important to raise professional awareness of early symptoms of EDs in children with a history of obesity and treat them accordingly.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_187,

title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.},

author = {Joshi PK and Pirastu N and Kentistou KA and Fischer K and Hofer E and {et al} and Biino G and {et al} and Hayward C and Chasman D and Martin NG and Sattar N and Campbell H and Esko T and Kutalik Z and Wilson JF},

url = {https://www.nature.com/articles/s41467-017-00934-5},

doi = {10.1038/s41467-017-00934-5},

year  = {2017},

date = {2017-10-13},

journal = {Nature Communications},

volume = {8},

number = {1},

pages = {910},

abstract = {Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_238,

title = {Relation between circulating oxidized-LDL and metabolic syndrome in children with obesity: the role of hypertriglyceridemic waist phenotype.},

author = {Calcaterra V and De Giuseppe R and Biino G and Mantelli M and Marchini S and Bendotti G and Madè A and Avanzini MA and Montalbano C and Cossellu G and Larizza D and Cena H},

url = {https://www.degruyter.com/view/j/jpem.ahead-of-print/jpem-2017-0239/jpem-2017-0239.xml},

doi = {doi.org/10.1515/jpem-2017-0239},

year  = {2017},

date = {2017-11-27},

journal = {Journal of pediatric endocrinology and metabolism},

volume = {30},

number = {12},

pages = {1257-1263},

abstract = {BACKGROUND: The association between oxidative stress (OS) and metabolic syndrome (MetS) has been reported in adults. We analyzed the relation between circulating oxidized low-density lipoproteins (Ox-LDL) and MetS in pediatric ages in order to define whether plasma Ox-LDL levels are correlated to obesity and whether oxidative damage, using serum Ox-LDL levels as a proxy, are associated with MetS. METHODS: We enrolled 178 children (11.8±2.6 years). On the basis of a body mass index (BMI) threshold, the subjects were classified as: normal weight BMI <75th percentile; overweight BMI 75-97th percentile; obese BMI >97th percentile. Patients were classified as having MetS if they met three or more of the following criteria for age and sex: BMI >97th percentile, triglyceride levels >95th percentile, high-density lipoprotein (HDL) cholesterol level <5th percentile, systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) >95th percentile and impaired glucose tolerance. RESULTS: Obese children showed increased MetS prevalence (p=0.001) and higher Ox-LDL levels compared to normal- and overweight subjects (p<0.05), with a limited relation between Ox-LDL and MetS (p=0.06). Waist-to-height ratio (W/HtR) (p=0.02), triglycerides (TG) (p=0.001) and LDL-cholesterol (p<0.001) resulted independent predictors of increased plasma Ox-LDL levels. CONCLUSIONS: Oxidative damage was correlated with a hypertriglyceridemic waist phenotype and can be a precocious marker of MetS and cardiometabolic risk in obese children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_260,

title = {Evaluation of eating habits and lifestyle in patients with obesity before and after bariatric surgery: a single Italian center experience.},

author = {Cena H and De Giuseppe R and Biino G and Persico F and Ciliberto A and Giovanelli A and Stanford FC},

url = {http://www.sciencedirect.com/science/article/pii/S0167488915002931},

doi = {10.1186/s40064-016-3133-1},

year  = {2016},

date = {2016-09-01},

journal = {Springerplus},

volume = {5},

number = {1},

pages = {1467},

abstract = {"The study evaluated and compared the eating habits and lifestyle of patients with moderate to severe obesity who have undergone Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG). METHODS: Food frequency (FF), food habits (FH), physical activity and life style (PA) as well as smoking habits (SH) were analyzed in 50 RYGB (25 M; aged: 24-64) and 50 SG patients (25 M; aged: 22-63) by means of a validated questionnaire, before (T0) and 6 months (T1) post bariatric surgery. A score for each section (FF, FH, PA, SH) was calculated. RESULTS: ANOVA analysis (age/sex adjusted): FF and FH scores improved at T1 (RYGB and SG: p < 0.001); PA score improved but not significantly; SH score did not change at T1 neither in RYGB nor in SG. Mixed models: FF and PA scores did not correlate with age, gender, weight, BMI, neither in RYGB nor in SG; FH score was negatively correlated both with weight (RYGB: p = 0.002) and BMI (SG: p = 0.003); SH score was positively correlated with age, in SG (p = 0.002); the correlation was stronger in females than in males (p = 0.004). CONCLUSIONS: Although dietary habits improved, patients did not change their physical activity level or their smoking habits. Patients should receive adequate lifestyle counseling to ensure the maximal benefit from bariatric surgery.

"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_284,

title = {External validation of the MetS score, a prediction tool for metabolic syndrome.},

author = {Graziano F and Grassi M and Bonati MT and Zanchetti A and Biino G},

url = {http://www.sciencedirect.com/science/article/pii/S093947531500263X},

doi = {10.1016/j.numecd.2015.12.014},

year  = {2016},

date = {2016-04-29},

journal = {Nutrition, Metabolism, and Cardiovascular Diseases : Nmcd. Letter To Editor},

volume = {26},

number = {4},

pages = {359-360},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_298,

title = {Genetic variants linked to education predict longevity.},

author = {Marioni RE and Ritchie SJ and Joshi PK and Hagenaars SP and Okbay A and Fischer K and Adams MJ and Hill WD and Davies G and {et al} nad and Biino G and {et al} and Benjamin DJ},

url = {http://www.pnas.org/content/early/2016/10/25/1605334113.long},

doi = {10.1073/pnas.1605334113},

year  = {2016},

date = {2016-02-27},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {113},

number = {47},

pages = {13366-13371},

abstract = {Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_250,

title = {Genome-wide analysis identifies 12 loci influencing human reproductive behavior.},

author = {Barban N and Jansen R and de Vlaming R and Vaez A and Mandemakers JJ and Tropf FC and Shen X and Wilson JF and Chasman DI and Nolte IM and {et al} and Biino G and {et al } and Koellinger PD and den Hoed M and Snieder H and Mills MC},

url = {http://www.nature.com/ng/journal/v48/n12/full/ng.3698.html},

doi = {10.1038/ng.3698},

year  = {2016},

date = {2016-02-25},

journal = {Nature Genetics},

volume = {48},

number = {12},

pages = {1462-1472},

abstract = {The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_302,

title = {Genome-wide association study identifies 74 loci associated with educational attainment.},

author = {Okbay A and Beauchamp JP and Fontana MA and Lee JJ and Pers TH and Rietveld CA and Turley P and Chen GB and Emilsson V and Meddens SF and Oskarsson S and Pickrell JK and Thom K and Timshel P and {et al} and Biino G and {et al} and Benjamin DJ},

url = {http://www.nature.com/nature/journal/v533/n7604/full/nature17671.html},

doi = {10.1038/nature17671},

year  = {2016},

date = {2016-02-29},

journal = {Nature},

volume = {533},

number = {7604},

pages = {539-542},

abstract = {Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_277,

title = {Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.},

author = {Fan Q and Verhoeven VJ and Wojciechowski R and Barathi VA and Hysi PG and Guggenheim JA and Höhn R and Vitart V and Khawaja AP and Yamashiro K and Hosseini SM and {et aò} and Biino G and Vaccargiu S and Fossarello M and Fleck B and Yazar S and Tideman JW and Tedja M and Deangelis MM and Morrison M and Farrer L and Zhou X and Chen W and Mizuki N and Meguro A and Makela KM},

url = {http://www.nature.com/ncomms/2016/160329/ncomms11008/full/ncomms11008.html},

doi = {10.1038/ncomms11008},

year  = {2016},

date = {2016-03-29},

journal = {Nature Communications},

volume = {7},

pages = {11008},

abstract = {Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10(-5)), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_326,

title = {A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.},

author = {Bouzigon E and Nadif R and Thompson EE and Concas MP and Kuldanek S and Du G and {et al} and Biino G and Dizier MH and Pin I and Matran R and Lathrop M and Pirastu M and Demenais F and Ober C},

url = {https://onlinelibrary.wiley.com/doi/full/10.1111/cea.12461},

doi = {10.1111/cea.12461},

year  = {2015},

date = {2015-02-11},

journal = {Clinical and Experimental Allergy },

volume = {45},

number = {4},

pages = {797-806},

abstract = {"BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE:

This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

 2014 John Wiley & Sons Ltd."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_335,

title = {APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans},

author = {Tkatchenko AV and Tkatchenko TV and Guggenheim JA and {et al} and Biino G and {et al} and Williams C},

url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005432},

doi = {10.1371/journal.pgen.1005432},

year  = {2015},

date = {2015-02-05},

journal = {Plos Genetics},

volume = {11},

number = {8},

pages = {e1005432},

abstract = {Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (""missing heritability""). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5'-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10-4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10-3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10-3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 +/- 2.2 D, p < 1.0 × 10-4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10-4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10-4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p < 1.0 × 10-4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10-4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the ""missing"" myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high level of evolutionary conservation of the signaling pathways underlying refractive eye development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_356,

title = {Dissecting metabolic syndrome components: data from an epidemiologic survey in a genetic isolate.},

author = {Biino G and Concas MP and Cena H and Parracciani D and Vaccargiu S and Cosso M and Marras F and D'Esposito V and Beguinot F and Pirastu M},

url = {https://springerplus.springeropen.com/articles/10.1186/s40064-015-1049-9},

doi = {10.1186/s40064-015-1049-9.},

year  = {2015},

date = {2015-02-12},

journal = {Springerplus},

volume = {4},

pages = {324},

abstract = {The metabolic syndrome (MetS) is a large-scale and expanding public-health and clinical threat worldwide. We investigated the determinants of MetS, assessed its prevalence and components and, estimated their genetic contribution, taking advantage of the special characteristics of Sardinian isolated populations. Inhabitants of 10 villages in Ogliastra region participated in a cross-sectional survey in 2002-2008 (n = 9,647). Blood samples, blood pressure (BP), anthropometry and, data from a standardized interview were collected. Prevalence of MetS was estimated by the direct method of standardization. Variables associated with the MetS were identified using multilevel logistic regression. Heritability was determined using variance component models. MetS Prevalence was 19.6% (95% CI 18.9-20.4%) according to NCEP-ATPIII, 24.8% (95% CI 24.0-25.6%) according to IDF and, 29% (95% CI 28.1-29.8%) according to AHA/NHLBI harmonized criteria, ranging from 9 to 26% among villages. The most prevalent combination was BP + HDL-cholesterol (HDL) + triglycerides (TRIG) (19%), followed by BP + HDL + waist circumference (WAIST) (17%) and, BP + HDL + TRIG + WAIST (13.6%). Heritability of MetS was 48% (p = 1.62 × 10(-25)), as the two most common combinations (BP + HDL + TRIG and BP + HDL + WAIST) showed heritability of 53 and 52%, respectively. The larger genetic components of the two most frequent combinations determining MetS deserve greater investigation in order to understand the underlying mechanisms. Besides, further studies are warranted to confirm these findings both in isolated and outbred populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_360,

title = {Epicardial fat thickness: threshold values and lifestyle association in male adolescents.},

author = {Cena H and Fonte ML and Casali PM and Maffoni S and Roggi C and Biino G},

url = {https://onlinelibrary.wiley.com/doi/full/10.1111/ijpo.227},

doi = {10.1111/ijpo.227},

year  = {2015},

date = {2015-04-10},

journal = {Pediatric Obesity},

volume = {10},

number = {2},

pages = {105-111},

abstract = {BACKGROUND: Obese adolescents with high proportion of visceral fat are at higher risk of developing the metabolic syndrome. OBJECTIVES: The study aims to investigate if echocardiographic epicardial fat thickness (EF) could be predictive of visceral obesity (VO) early in life and to provide EF threshold values specific for male adolescents. Further aim was to investigate the association between EF, lifestyle and metabolic disease familiarity. METHODS: Anthropometric data were collected from 102 normal weight and overweight, healthy male adolescents (mean age: 14.91 +/-  1.98 years); bioelectrical impedance analysis and transthoracic echocardiogram were performed in the same sample. Each participant fulfilled a validated self-administered lifestyle questionnaire. RESULTS: We found higher EF values in sedentary adolescents (P < 0.05), in those who never eat fruit and vegetables (P < 0.05), and in those with overweight mothers (P < 0.05). The strongest independent predictor of EF was waist circumference (P < 0.0001). Using the waist to height ratio as a marker of VO, logistic regression analysis revealed that 1 mm EF gain is responsible for seven times higher VO risk (P < 0.0001). Receiver Operating Characteristic (ROC) analysis showed that the optimal cut-off for EF thickness associated to youth VO is 3.2 mm.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_364,

title = {Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss.},

author = {Vuckovic D and Dawson S and Scheffer DI and Rantanen T and Morgan A and Di Stazio M and Vozzi D and Nutile T and Concas MP and Biino G and Nolan L and Bahl A and Loukola A and Viljanen A and Davis A and Ciullo M and Corey DP and Pirastu M and Gasparini P and Girotto G},

url = {https://academic.oup.com/hmg/article/24/19/5655/584102},

doi = {10.1093/hmg/ddv279},

year  = {2015},

date = {2015-10-01},

journal = {Human Molecular Genetics },

volume = {24},

number = {19},

pages = {5655-5664},

abstract = {Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_366,

title = {Height-reducing variants and selection for short stature in Sardinia.},

author = {Zoledziewska M and Sidore C and Chiang CW and Sanna S and Mulas A and Steri M and Busonero F and Marcus JH and Marongiu M and Maschio A and Del Vecchyo DO and Floris M and Meloni A and Delitala A and Concas MP and Murgia F and Biino G and Vaccargiu S and Nagaraja R and Lohmueller KE and UK10K Consortium and Timpson NJ and Soranzo N and Tachmazidou I and Dedoussis G and Zeggini E and Understanding Society Scientific Group and Uzzau S and Jones C and Lyons R and Angius A and Abecasis GR and Novembre J and Schlessinger D and Cucca F},

url = {https://www.nature.com/articles/ng.3403},

doi = {10.1038/ng.3403},

year  = {2015},

date = {2015-11-25},

journal = {Nature Genetics},

volume = {47},

number = {11},

pages = {1352-1356},

abstract = {We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (-0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (-0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_391,

title = {Personalized reference intervals for platelet count reduce the number of subjects with unexplained thrombocytopenia.},

author = {Zaninetti C and Biino G and Noris P and Melazzini F and Civaschi E and Balduini CL},

url = {http://www.haematologica.org/content/100/9/e338.long},

doi = {10.3324/haematol.2015.127597},

year  = {2015},

date = {2015-09-26},

journal = {Haematologica},

volume = {100},

number = {9},

pages = {e338-340},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_397,

title = {Probing the factor structure of metabolic syndrome in Sardinian genetic isolates.},

author = {Graziano F and Grassi M and Sacco S and Concas MP and Vaccargiu S and Pirastu M and Biino G},

url = {https://www.sciencedirect.com/science/article/pii/S0939475315000472?via%3Dihub},

doi = {10.1016/j.numecd.2015.02.004},

year  = {2015},

date = {2015-06-26},

journal = {Nutrition, Metabolism, and Cardiovascular Diseases : Nmcd. Letter To Editor},

volume = {25},

pages = {548-555},

abstract = {BACKGROUND AND AIMS: Owing to the multiplicity of the key components of metabolic syndrome (MetS), its diagnosis is very complex. The lack of a unique definition is responsible for the prevalence variability observed among studies; therefore, a definition based on continuous variables was recommended. The aim of this study was to compare competing models of the MetS factor structure for selecting the one that explains the best clustering pattern and to propose an algorithm for computing MetS as a continuous variable. METHODS AND RESULTS: Data were from isolated Sardinian populations (n = 8102). Confirmatory factor analysis (CFA) and two-group CFA by gender were performed to evaluate the sex-specific factor structure of MetS. After selecting the best model, an algorithm was obtained using factor loadings/residual variances. The quality of the MetS score was evaluated by the receiver operating characteristics curve and the area under the curve. Cross-validation was performed to validate the score and to determine the best cut point. The best fit model was a bifactor one with a general factor (MetS) and three specific factors (f1: obesity/adiposity trait; f2: hypertension/blood pressure trait; and f3: lipid trait). Gender-specific algorithms were implemented to obtain MetS scores showing a good diagnostic performance (0.80 specificity and 0.80 sensitivity for the cut point). Furthermore, cross-validation confirmed these results. CONCLUSION: These analyses suggested that the bifactor model was the most representative one. In addition, they provided a score and a cut point that are both clinically accessible and interpretable measures for MetS diagnosis and likely useful for evaluating the association with adverse cardiovascular disease and diabetes and for investigating the MetS genetic component.Copyright © 2015 Elsevier B.V. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}