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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Deelen, J; Evans, DS; Arking, DE; Tesi, N; Nygaard, M; Liu, X; Wojczynski, MK; Biggs, ML; van der Spek, A; Atzmon, G; Ware, EB; Sarnowski, C; Smith, AV; Seppälä, I; Cordell, HJ; Dose, J; Amin, N; Arnold, AM; Ayers, KL; Barzilai, N; Becker, EJ; Beekman, M; Blanché, H; Christensen, K; Christiansen, L; Collerton, JC; Cubaynes, S; Cummings, SR; Davies, K; Debrabant, B; Deleuze, J-F; Duncan, R; Faul, JD; Franceschi, C; Galan, P; Gudnason, V; Harris, TB; Huisman, M; Hurme, MA; Jagger, C; Jansen, I; Jylhä, M; Kähönen, M; Karasik, D; Kardia, SLR; Kingston, A; Kirkwood, TBL; Launer, LJ; Lehtimäki, T; Lieb, W; Lyytikäinen, L-P; Martin-Ruiz, C; Min, J; Nebel, A; Newman, AB; Nie, C; Nohr, EA; Orwoll, ES; Perls, TT; Province, MA; Psaty, BM; Raitakari, OT; Reinders, MJT; Robine, J-M; Rotter, JI; Sebastiani, P; Smith, J; Sørensen, TIA; Taylor, KD; Uitterlinden, AG; van der Flier, W; van der Lee, SJ; van Duijn, CM; van Heemst, D; Vaupel, JW; Weir, D; Ye, K; Zeng, Y; Zheng, W; Holstege, H; Kiel, DP; Lunetta, KL; Slagboom, PE; Murabito, JM

Published Date

  • August 14, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 3669 -

PubMed ID

  • 31413261

Pubmed Central ID

  • 31413261

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-11558-2

Language

  • eng

Conference Location

  • England