A meta-analysis of genome-wide association studies identifies multiple longevity genes-Reference-Cited by-同舟云学术

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

Published:2019-08-14 Issue:1 Volume:10 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Deelen Joris^ORCID,Evans Daniel S.,Arking Dan E.,Tesi Niccolò^ORCID,Nygaard Marianne^ORCID,Liu Xiaomin^ORCID,Wojczynski Mary K.,Biggs Mary L.,van der Spek Ashley^ORCID,Atzmon Gil,Ware Erin B.^ORCID,Sarnowski Chloé,Smith Albert V.,Seppälä Ilkka^ORCID,Cordell Heather J.^ORCID,Dose Janina,Amin Najaf,Arnold Alice M.,Ayers Kristin L.,Barzilai Nir,Becker Elizabeth J.,Beekman Marian^ORCID,Blanché Hélène^ORCID,Christensen Kaare^ORCID,Christiansen Lene,Collerton Joanna C.,Cubaynes Sarah,Cummings Steven R.,Davies Karen,Debrabant Birgit,Deleuze Jean-François,Duncan Rachel,Faul Jessica D.,Franceschi Claudio,Galan Pilar^ORCID,Gudnason Vilmundur^ORCID,Harris Tamara B.,Huisman Martijn,Hurme Mikko A.,Jagger Carol^ORCID,Jansen Iris,Jylhä Marja,Kähönen Mika,Karasik David^ORCID,Kardia Sharon L. R.,Kingston Andrew,Kirkwood Thomas B. L.,Launer Lenore J.,Lehtimäki Terho,Lieb Wolfgang,Lyytikäinen Leo-Pekka,Martin-Ruiz Carmen^ORCID,Min Junxia,Nebel Almut,Newman Anne B.^ORCID,Nie Chao,Nohr Ellen A.,Orwoll Eric S.^ORCID,Perls Thomas T.,Province Michael A.,Psaty Bruce M.,Raitakari Olli T.,Reinders Marcel J. T.^ORCID,Robine Jean-Marie^ORCID,Rotter Jerome I.^ORCID,Sebastiani Paola,Smith Jennifer^ORCID,Sørensen Thorkild I. A.^ORCID,Taylor Kent D.^ORCID,Uitterlinden André G.^ORCID,van der Flier Wiesje,van der Lee Sven J.^ORCID,van Duijn Cornelia M.,van Heemst Diana,Vaupel James W.,Weir David^ORCID,Ye Kenny^ORCID,Zeng Yi,Zheng Wanlin,Holstege Henne,Kiel Douglas P.^ORCID,Lunetta Kathryn L.^ORCID,Slagboom P. Eline,Murabito Joanne M.

Abstract

AbstractHuman 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.

Funder

Alexander von Humboldt-Stiftung

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

http://www.nature.com/articles/s41467-019-11558-2.pdf

Reference62 articles.

1. Oeppen, J. & Vaupel, J. W. Demography. Broken limits life Expect. Sci. 296, 1029–1031 (2002).

2. van den Berg, N., Beekman, M., Smith, K. R., Janssens, A. & Slagboom, P. E. Historical demography and longevity genetics: back to the future. Ageing Res. Rev. 38, 28–39 (2017).

3. Kaplanis, J. et al. Quantitative analysis of population-scale family trees with millions of relatives. Science 360, 171–175 (2018).