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

TitreGenome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
Publication TypeJournal Article
Year of Publication2017
AuthorsJoshi, PK, Pirastu, N, Kentistou, KA, Fischer, K, Hofer, E, Schraut, KE, Clark, DW, Nutile, T, Barnes, CLK, Timmers, PRHJ, Shen, X, Gandin, I, McDaid, A, Hansen, TFolkmann, 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, MPina, Biino, G, Tajuddin, SM, älä, I, Amin, N, Boerwinkle, E, ørglum, AD, Campbell, A, Demerath, EW, Demuth, I, Faul, JD, Ford, I, Gialluisi, A, ögele, M, Graff, M, Hingorani, A, Hottenga, J-J, Hougaard, DM, Hurme, MA, M. Ikram, A, ä, M, Kuh, D, Ligthart, L, Lill, CM, Lindenberger, U, Lumley, T, ägi, 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, P. Slagboom, E, Smith, BH, Smith, JA, Sotoodehnia, N, Steinhagen-Thiessen, E, van Rooij, FJA, Verbeek, éL, Vermeulen, SH, Vollenweider, P, Wang, Y, Werge, T, Whitfield, JB, Zonderman, AB, äki, 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, J. Jukema, W, Kiemeney, L, Uitterlinden, éG, Franceschini, N, North, KE, Weir, DR, Metspalu, A, Boomsma, DI, Hayward, C, Chasman, D, Martin, NG, Sattar, N, Campbell, H, Esko, ōnu, Kutalik, Z, Wilson, JF
JournalNature Communications
Volume8
Issue1
Pagination910
Date Published10/2017
URLhttps://www.nature.com/articles/s41467-017-00934-5
DOI10.1038/s41467-017-00934-5
ISSN2041-1723
Accession NumberPMID:29030599
Mots-clésAlleles, Body Mass Index, Coronary Disease/blood, Coronary Disease/etiology, Education, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, HDL/blood, HLA-DQ alpha-Chains/genetics, HLA-DRB1 Chains/genetics, Humans, Insulin Resistance/genetics, Life Style, Lipoprotein(a)/genetics, Lipoproteins, Longevity/genetics, Lung Neoplasms/blood, Lung Neoplasms/genetics, Obesity/complications, Obesity/genetics, polymorphism, Single Nucleotide, Smoking/adverse effects, Socioeconomic Factors
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.

WOS ID (UT)

000412871300006

Short TitleNat Commun
Citation Key / SERVAL ID8264
Peer reviewRefereed

                         

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