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

TitleA meta-analysis of genome-wide association studies identifies multiple longevity genes.
Publication TypeJournal Article
Year of Publication2019
AuthorsDeelen, 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, AVernon, 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, J, 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, JA, Sørensen, TIA, Taylor, KD, Uitterlinden, AG, van der Flier, W, van der Lee, SJ, van Duijn, CM, van Heemst, D, Vaupel, JW, Weir, DR, Ye, K, Zeng, Y, Zheng, W, Holstege, H, Kiel, DP, Lunetta, KL, Slagboom, EP, Murabito, JM
JournalNature Communications
Volume10
Issue1
Pagination3669
Date Published08/2019
ISSN Number2041-1723
Keywordsgenes, Genome-Wide Association Study, GWA, longevity genes, meta-analysis
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.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/31413261
DOI10.1038/s41467-019-11558-2
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/31413261?dopt=Abstract

Alternate JournalNat Commun
Citation Key10225
PubMed ID31413261
PubMed Central IDPMC6694136
Grant List102858/Z/13/Z / WT_ / Wellcome Trust / United Kingdom
MR/J50001X/1 / MRC_ / Medical Research Council / United Kingdom
UL1 TR002369 / TR / NCATS NIH HHS / United States
G0500997 / MRC_ / Medical Research Council / United Kingdom
S10 OD016290 / OD / NIH HHS / United States
R01 AG055406 / AG / NIA NIH HHS / United States
L60 MD012145 / MD / NIMHD NIH HHS / United States