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

Lookup NU author(s): Professor Heather Cordell, Dr Joanna Collerton, Dr Karen Davies, Dr Rachel Duncan, Professor Carol Jagger, Dr Andrew Kingston, Dr Carmen Martin-Ruiz

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2019, The Author(s).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.


Publication metadata

Author(s): 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, Seppala I, Cordell HJ, Dose J, Amin N, Arnold AM, Ayers KL, Barzilai N, Becker EJ, Beekman M, Blanche 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, Jylha M, Kahonen M, Karasik D, Kardia SLR, Kingston A, Kirkwood TBL, Launer LJ, Lehtimaki T, Lieb W, Lyytikainen 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, Sorensen 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

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2019

Volume: 10

Issue: 1

Online publication date: 14/08/2019

Acceptance date: 17/07/2019

Date deposited: 28/08/2019

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41467-019-11558-2

DOI: 10.1038/s41467-019-11558-2


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