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

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11558-2

2041-1723

Joris Deelen, Daniel S. Evans, Dan E. Arking, Niccoló Tesi, Marianne Nygaard, Xiaomin Liu, Mary K. Wojczynski, Mary L. Biggs, Ashley van der Spek, Gil Atzmon, Erin B. Ware, Chloé Sarnowski, Albert V. Smith, Ilkka Seppälä, Heather J. Cordell, Janina Dose, Najaf Amin, Alice M. Arnold, Kristin L. Ayers, Nir Barzilai, Elizabeth J. Becker, Marian Beekman, Hélène Blanché, Kaare Christensen, Lene Christiansen, Joanna Collerton, Sarah Cubaynes, Steven R. Cummings, Karen Davies, Birgit Debrabant, Jean‐François Deleuze, Rachel Duncan, Jessica D. Faul, Claudio Franceschi, Pilar Galán, Vilmundur Guðnason, Tamara B. Harris, Martijn Huisman, Mikko Hurme, Carol Jagger, Iris E. Jansen, Marja Jylhä, Mika Kähönen, David Karasik, Sharon L. R. Kardia, Andrew Kingston, Thomas B. L. Kirkwood, Lenore J. Launer, Terho Lehtimäki, Wolfgang Lieb, Leo‐Pekka Lyytikäinen, Carmen Martin‐Ruiz, Junxia Min, Almut Nebel, Anne B. Newman, Chao Nie, Ellen A. Nøhr, Eric Orwoll, Thomas T. Perls, Michael A. Province, Bruce M. Psaty, Olli Raitakari, Marcel J. T. Reinders, Jean‐Marie Robine, Jerome I. Rotter, Paola Sebastiani, Jennifer A. Smith, Thorkild I. A. Sörensen, Kent D. Taylor, André G. Uitterlinden, Wiesje M. van der Flier, Sven J. van der Lee, Cornelia M. van Duijn, Diana van Heemst, James W. Vaupel, David R. Weir, Kenny Ye, Yi Zeng, Wanlin Zheng, Henne Holstege, Douglas P. Kiel, Kathryn L. Lunetta, P. Eline Slagboom, Joanne M. Murabito,

Genetics, Aging, and Longevity in Model Organisms

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.