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

J Deelen, Evans D., Arking Dan E., Niccolo Tesi, Nygaard M, Xiaoming Liu, Wojczynski Mary K., Marcel Reinders, Henne Holstege, More Authors

Research output: Contribution to journalArticleScientificpeer-review

61 Citations (Scopus)
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Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limitedsuccess. Here, we perform two meta-analyses of GWA studies of a rigorous longevityphenotype definition including 11,262/3484 cases surviving at or beyond the age corre-sponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose ageat death or at last contact was at or below the age corresponding to the 60th survivalpercentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE)ε4) isassociated with lower odds of surviving to the 90th and 99th percentile age, while rs7412(ApoEε2) shows the opposite. Moreover, rs7676745, located nearGPR78, associates withlower odds of surviving to the 90th percentile age. Gene-level association analysis reveals arole for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation ofthe longevity GWA results with that of several disease-related phenotypes points to a sharedgenetic architecture between health and longevity
Original languageEnglish
Article number3669
Number of pages14
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019

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