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Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.

Autori

Joshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers PRHJ, Shen X, Gandin I, McDaid AF, Hansen TF, Gordon SD, Giulianini F, Boutin TS, Abdellaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Concas MP, Biino G, Tajuddin SM, Seppala I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, Gogele M, Graff M, Hingorani A, Hottenga JJ, Hougaard DM, Hurme MA, Ikram MA, Jylha M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, Mägi R, Marques-Vidal P, Medland SE, Milani L, Nagy R, Ollier WER, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slagboom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtimäki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM, van Duijn CM, Wilson JG, Jukema JW, Kiemeney L, Uitterlinden AG, Franceschini N, North KE, Weir DR, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF.

Riferimenti

Nature Communications 8(1) 910-, 2017

Autori CNR

BIINO

Moduli

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.

Link all articolo

https://www.nature.com/articles/s41467-017-00934-5

Parole Chiave

Note

10.1038/s41467-017-00934-5

Indietro


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