A meta-analysis of genome-wide association studies identifies multiple longevity genes

Joris Deelen(Leiden University Medical Center), Daniel S. Evans(California Pacific Medical Center), Dan E. Arking(Johns Hopkins University), Niccoló Tesi(Amsterdam UMC Location University of Amsterdam), Marianne Nygaard(University of Southern Denmark), Xiaomin Liu(BGI Group (China)), Mary K. Wojczynski(Washington University in St. Louis), Mary L. Biggs(University of Washington), Ashley van der Spek(Erasmus MC), Gil Atzmon(Oranim Academic College of Education), Erin B. Ware(Inslaw (United States)), Chloé Sarnowski(Boston University), Albert V. Smith(University of Michigan), Ilkka Seppälä(Tampere University of Applied Sciences), Heather J. Cordell(Centre for Life), Janina Dose(Christian-Albrechts-Universität zu Kiel), Najaf Amin(Erasmus MC), Alice M. Arnold(University of Washington), Kristin L. Ayers(Sema4 (United States)), Nir Barzilai(Albert Einstein College of Medicine), Elizabeth J. Becker(Boston University), Marian Beekman(Leiden University Medical Center), Hélène Blanché(Fondation Jean Dausset-CEPH), Kaare Christensen(University of Southern Denmark), Lene Christiansen(University of Southern Denmark), Joanna Collerton(Royal Victoria Infirmary), Sarah Cubaynes(Inserm), Steven R. Cummings(California Pacific Medical Center), Karen Davies(Newcastle University), Birgit Debrabant(University of Southern Denmark), Jean‐François Deleuze(Commissariat à l'Énergie Atomique et aux Énergies Alternatives), Rachel Duncan(Newcastle University), Jessica D. Faul(Inslaw (United States)), Claudio Franceschi(Institute of Neurological Sciences), Pilar Galán(Inserm), Vilmundur Guðnason(University of Iceland), Tamara B. Harris(National Institute on Aging), Martijn Huisman(Public Health Service of Amsterdam), Mikko Hurme(Tampere University of Applied Sciences), Carol Jagger(Newcastle Hospitals - Campus for Ageing and Vitality), Iris E. Jansen(Amsterdam Neuroscience), Marja Jylhä(Tampere University), Mika Kähönen(Tampere University Hospital), David Karasik(Bar-Ilan University), Sharon L. R. Kardia(University of Michigan), Andrew Kingston(Royal Victoria Infirmary), Thomas B. L. Kirkwood(Newcastle University), Lenore J. Launer(National Institute on Aging), Terho Lehtimäki(Tampere University of Applied Sciences), Wolfgang Lieb(Hochschule für Angewandte Wissenschaften Kiel), Leo‐Pekka Lyytikäinen(Tampere University of Applied Sciences), Carmen Martín-Ruiz(Newcastle University), Junxia Min(Zhejiang University), Almut Nebel(Christian-Albrechts-Universität zu Kiel), Anne B. Newman(University of Pittsburgh), Chao Nie(BGI Group (China)), Ellen A. Nøhr(University of Southern Denmark), Eric Orwoll(Oregon Health & Science University), Thomas T. Perls(Boston University), Michael A. Province(Washington University in St. Louis), Bruce M. Psaty(Kaiser Permanente Washington Health Research Institute), Olli Raitakari(University of Turku), Marcel Reinders(Delft University of Technology), Jean‐Marie Robine(Délégation Paris 5), Jerome I. Rotter(The Lundquist Institute), Paola Sebastiani(Boston University), Jennifer A. Smith(University of Michigan), Thorkild I. A. Sørensen(Paris-Est Sup), Kent D. Taylor(The Lundquist Institute), André G. Uitterlinden(Erasmus MC), Wiesje M. van der Flier(Amsterdam Neuroscience), Sven J. van der Lee(Amsterdam UMC Location University of Amsterdam), Cornelia M. van Duijn(Erasmus MC), Diana van Heemst(Leiden University Medical Center), James W. Vaupel(Max Planck Institute for Demographic Research), David R. Weir(University of Michigan), Kenny Ye(Albert Einstein College of Medicine), Yi Zeng(Duke University), Wanlin Zheng(California Pacific Medical Center), Henne Holstege(Amsterdam UMC Location University of Amsterdam), Douglas P. Kiel(Broad Institute), Kathryn L. Lunetta(Boston University), P. Eline Slagboom(Leiden University Medical Center), Joanne M. Murabito(Boston University)
Nature Communications
August 14, 2019
10.1038/s41467-019-11558-2
Cited by 400Open Access
Full Text

Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Related Papers

No related papers found

Powered by citation graph analysis