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

Joris Deelen (), Daniel S. Evans (), Dan E. Arking, Niccolò Tesi, Marianne Nygaard, Xiaomin Liu, Mary K. Wojczynski, Mary L. Biggs, Ashley van der Spek, Gil Atzmon, Erin B. Ware, Chloé Sarnowski, Albert V. Smith, Ilkka Seppälä, Heather J. Cordell, Janina Dose, Najaf Amin, Alice M. Arnold, Kristin L. Ayers, Nir Barzilai, Elizabeth J. Becker, Marian Beekman, Hélène Blanché, Kaare Christensen, Lene Christiansen, Joanna C. Collerton, Sarah Cubaynes, Steven R. Cummings, Karen Davies, Birgit Debrabant, Jean-François Deleuze, Rachel Duncan, Jessica D. Faul, Claudio Franceschi, Pilar Galan, Vilmundur Gudnason, Tamara B. Harris, Martijn Huisman, Mikko A. Hurme, Carol Jagger, Iris Jansen, Marja Jylhä, Mika Kähönen, David Karasik, Sharon L. R. Kardia, Andrew Kingston, Thomas B. L. Kirkwood, Lenore J. Launer, Terho Lehtimäki, Wolfgang Lieb, Leo-Pekka Lyytikäinen, Carmen Martin-Ruiz, Junxia Min, Almut Nebel, Anne B. Newman, Chao Nie, Ellen A. Nohr, Eric S. Orwoll, Thomas T. Perls, Michael A. Province, Bruce M. Psaty, Olli T. Raitakari, Marcel J. T. Reinders, Jean-Marie Robine, Jerome I. Rotter, Paola Sebastiani, Jennifer Smith, Thorkild I. A. Sørensen, Kent D. Taylor, André G. Uitterlinden, Wiesje van der Flier, Sven J. van der Lee, Cornelia M. van Duijn, Diana van Heemst, James W. Vaupel, David Weir, Kenny Ye, Yi Zeng, Wanlin Zheng, Henne Holstege, Douglas P. Kiel, Kathryn L. Lunetta, P. Eline Slagboom () and Joanne M. Murabito ()
Additional contact information
Joris Deelen: Max Planck Institute for Biology of Ageing
Daniel S. Evans: California Pacific Medical Center Research Institute
Dan E. Arking: Johns Hopkins University School of Medicine
Niccolò Tesi: Vrije Universiteit Amsterdam, Amsterdam UMC
Marianne Nygaard: University of Southern Denmark
Xiaomin Liu: BGI-Shenzhen
Mary K. Wojczynski: Washington University School of Medicine
Mary L. Biggs: University of Washington
Ashley van der Spek: Erasmus MC
Gil Atzmon: University of Haifa
Erin B. Ware: University of Michigan
Chloé Sarnowski: Boston University School of Public Health
Albert V. Smith: University of Michigan
Ilkka Seppälä: Tampere University
Heather J. Cordell: Newcastle University
Janina Dose: Kiel University
Najaf Amin: Erasmus MC
Alice M. Arnold: University of Washington
Kristin L. Ayers: Sema4, a Mount Sinai venture
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 C. Collerton: Newcastle University
Sarah Cubaynes: MMDN, Univ. Montpellier, EPHE, Unité Inserm 1198, PSL Research University
Steven R. Cummings: California Pacific Medical Center Research Institute
Karen Davies: Newcastle University
Birgit Debrabant: University of Southern Denmark
Jean-François Deleuze: Fondation Jean Dausset—CEPH
Rachel Duncan: Newcastle University
Jessica D. Faul: University of Michigan
Claudio Franceschi: Lobachevsky State University of Nizhny Novgorod
Pilar Galan: EREN, UMR U1153 Inserm/U1125 Inra/Cnam/Paris 13, Université Paris 13, CRESS
Vilmundur Gudnason: Icelandic Heart Association
Tamara B. Harris: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH
Martijn Huisman: Vrije Universiteit Amsterdam, Amsterdam UMC
Mikko A. Hurme: Faculty of Medicine and Health Technology, Tampere University
Carol Jagger: Newcastle University
Iris Jansen: Vrije Universiteit Amsterdam, Amsterdam UMC
Marja Jylhä: Tampere University
Mika Kähönen: Tampere University Hospital and Finnish Cardiovascular Research Center—Tampere, Faculty of Medicine and Health Technology, Tampere University
David Karasik: Bar Ilan University
Sharon L. R. Kardia: University of Michigan
Andrew Kingston: Newcastle University
Thomas B. L. Kirkwood: Newcastle University Institute for Ageing, Newcastle University
Lenore J. Launer: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH
Terho Lehtimäki: Tampere University
Wolfgang Lieb: Kiel University
Leo-Pekka Lyytikäinen: Tampere University
Carmen Martin-Ruiz: Newcastle University
Junxia Min: Zhejiang University
Almut Nebel: Kiel University
Anne B. Newman: University of Pittsburgh
Chao Nie: BGI-Shenzhen
Ellen A. Nohr: University of Southern Denmark
Eric S. Orwoll: Oregon Health Sciences University
Thomas T. Perls: Boston University School of Medicine
Michael A. Province: Washington University School of Medicine
Bruce M. Psaty: University of Washington
Olli T. Raitakari: Turku University Hospital
Marcel J. T. Reinders: Delft University of Technology
Jean-Marie Robine: MMDN, Univ. Montpellier, EPHE, Unité Inserm 1198, PSL Research University
Jerome I. Rotter: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Paola Sebastiani: Boston University School of Public Health
Jennifer Smith: University of Michigan
Thorkild I. A. Sørensen: University of Copenhagen
Kent D. Taylor: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
André G. Uitterlinden: Erasmus MC
Wiesje van der Flier: Vrije Universiteit Amsterdam, Amsterdam UMC
Sven J. van der Lee: Vrije Universiteit Amsterdam, Amsterdam UMC
Cornelia M. van Duijn: Erasmus MC
Diana van Heemst: Leiden University Medical Center
James W. Vaupel: Max Planck Institute for Demographic Research
David Weir: University of Michigan
Kenny Ye: Albert Einstein College of Medicine
Yi Zeng: Peking University
Wanlin Zheng: California Pacific Medical Center Research Institute
Henne Holstege: Vrije Universiteit Amsterdam, Amsterdam UMC
Douglas P. Kiel: Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife
Kathryn L. Lunetta: Boston University School of Public Health
P. Eline Slagboom: Leiden University Medical Center
Joanne M. Murabito: NHLBI’s and Boston University’s Framingham Heart Study

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11558-2

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