A meta-analysis of genome-wide association studies identifies multiple longevity genes
J Deelen (Max Planck Institute for Biology of Ageing, Leiden University Medical Center)
Evans D. (California Pacific Medical Center Research Institute, San Francisco)
Arking Dan E. (Johns Hopkins University)
Niccolo Tesi (TU Delft - Electrical Engineering, Mathematics and Computer Science)
Nygaard M (University of Southern Denmark)
Xiaoming Liu (BGI-Shenzhen, Shenzhen)
Wojczynski Mary K. (Washington University School of Medicine)
Marcel Reinders (TU Delft - Electrical Engineering, Mathematics and Computer Science)
Henne Holstege (TU Delft - Electrical Engineering, Mathematics and Computer Science)
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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
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