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Nature Research, Nature Communications, 1(10), 2019

DOI: 10.1038/s41467-019-11558-2



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

Journal article published in 2019 by Joris Deelen ORCID, Daniel S. Evans, Dan E. Arking, Niccolò Tesi ORCID, Marianne Nygaard ORCID, Xiaomin Liu ORCID, Mary K. Wojczynski, Mary L. Biggs, Ashley van der Spek ORCID, Gil Atzmon, Erin B. Ware ORCID, Chloé Sarnowski ORCID, Albert V. Smith, Ilkka Seppälä ORCID, Heather J. Cordell ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.