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

Joshi, P.K.; Pirastu, N.; Kentistou, K.A.; Fischer, K.; Hofer, E.; Schraut, K.E.; Clark, D.W.; Nutile, T.; Barnes, CLK; Timmers, PRHJ; Shen, X.; Gandin, I.; McDaid, A.F.; Hansen, T.F.; Gordon, S.D.; Giulianini, F.; Boutin, T.S.; Abdellaoui, A.; Zhao, W.; Medina-Gomez, C.; Bartz, T.M.; Trompet, S.; Lange, L.A.; Raffield, L.; van der Spek, A.; Galesloot, T.E.; Proitsi, P.; Yanek, L.R.; Bielak, L.F.; Payton, A.; Murgia, F.; Concas, M.P.; Biino, G.; Tajuddin, S.M.; Seppälä, I.; Amin, N.; Boerwinkle, E.; Børglum, A.D.; Campbell, A.; Demerath, E.W.; Demuth, I.; Faul, J.D.; Ford, I.; Gialluisi, A.; Gögele, M.; Graff, M.; Hingorani, A.; Hottenga, J.J.; Hougaard, D.M.; Hurme, M.A.; Ikram, M.A.; Jylhä, M.; Kuh, D.; Ligthart, L.; Lill, C.M.; Lindenberger, U.; Lumley, T.; Mägi, R.; Marques-Vidal, P.; Medland, S.E.; Milani, L.; Nagy, R.; Ollier, WER; Peyser, P.A.; Pramstaller, P.P.; Ridker, P.M.; Rivadeneira, F.; Ruggiero, D.; Saba, Y.; Schmidt, R.; Schmidt, H.; Slagboom, P.E.; Smith, B.H.; Smith, J.A.; Sotoodehnia, N.; Steinhagen-Thiessen, E.; van Rooij, FJA; Verbeek, A.L.; Vermeulen, S.H.; Vollenweider, P.; Wang, Y.; Werge, T.; Whitfield, J.B.; Zonderman, A.B.; Lehtimäki, T.; Evans, M.K.; Pirastu, M.; Fuchsberger, C.; Bertram, L.; Pendleton, N.; Kardia, SLR; Ciullo, M.; Becker, D.M.; Wong, A.; Psaty, B.M.; van Duijn, C.M.; Wilson, J.G.; Jukema, J.W.; Kiemeney, L.; Uitterlinden, A.G.; Franceschini, N.; North, K.E.; Weir, D.R.; Metspalu, A.; Boomsma, D.I.; Hayward, C.; Chasman, D.; Martin, N.G.; Sattar, N.; Campbell, H.; Esko, T.; Kutalik, Z.; Wilson, J.F.

doi:10.1038/s41467-017-00934-5

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

Details

Download: BIB_AA3220915510.pdf (2130.75 [Ko])
State: Public
Version: Final published version

Serval ID

serval:BIB_AA3220915510

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature communications

Author(s)

Joshi P.K., Pirastu N., Kentistou K.A., Fischer K., Hofer E., Schraut K.E., Clark D.W., Nutile T., Barnes CLK, Timmers PRHJ, Shen X., Gandin I., McDaid A.F., Hansen T.F., Gordon S.D., Giulianini F., Boutin T.S., Abdellaoui A., Zhao W., Medina-Gomez C., Bartz T.M., Trompet S., Lange L.A., Raffield L., van der Spek A., Galesloot T.E., Proitsi P., Yanek L.R., Bielak L.F., Payton A., Murgia F., Concas M.P., Biino G., Tajuddin S.M., Seppälä I., Amin N., Boerwinkle E., Børglum A.D., Campbell A., Demerath E.W., Demuth I., Faul J.D., Ford I., Gialluisi A., Gögele M., Graff M., Hingorani A., Hottenga J.J., Hougaard D.M., Hurme M.A., Ikram M.A., Jylhä M., Kuh D., Ligthart L., Lill C.M., Lindenberger U., Lumley T., Mägi R., Marques-Vidal P., Medland S.E., Milani L., Nagy R., Ollier WER, Peyser P.A., Pramstaller P.P., Ridker P.M., Rivadeneira F., Ruggiero D., Saba Y., Schmidt R., Schmidt H., Slagboom P.E., Smith B.H., Smith J.A., Sotoodehnia N., Steinhagen-Thiessen E., van Rooij FJA, Verbeek A.L., Vermeulen S.H., Vollenweider P., Wang Y., Werge T., Whitfield J.B., Zonderman A.B., Lehtimäki T., Evans M.K., Pirastu M., Fuchsberger C., Bertram L., Pendleton N., Kardia SLR, Ciullo M., Becker D.M., Wong A., Psaty B.M., van Duijn C.M., Wilson J.G., Jukema J.W., Kiemeney L., Uitterlinden A.G., Franceschini N., North K.E., Weir D.R., Metspalu A., Boomsma D.I., Hayward C., Chasman D., Martin N.G., Sattar N., Campbell H., Esko T., Kutalik Z., Wilson J.F.

ISSN

2041-1723 (Electronic)

ISSN-L

2041-1723

Publication state

Published

Issued date

13/10/2017

Peer-reviewed

Oui

Volume

Number

Pages

910

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish

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

Alleles, Body Mass Index, Coronary Disease/blood, Coronary Disease/etiology, Education, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, HLA-DQ alpha-Chains/genetics, HLA-DRB1 Chains/genetics, Humans, Insulin Resistance/genetics, Life Style, Lipoprotein(a)/genetics, Lipoproteins, HDL/blood, Longevity/genetics, Lung Neoplasms/blood, Lung Neoplasms/genetics, Obesity/complications, Obesity/genetics, Polymorphism, Single Nucleotide, Smoking/adverse effects, Socioeconomic Factors

URN

urn:nbn:ch:serval-BIB_AA32209155100

OAI-PMH

oai:serval.unil.ch:BIB_AA3220915510

DOI

10.1038/s41467-017-00934-5

Pubmed

29030599

Web of science

000412871300006

Open Access

Yes