A meta-analysis of genome-wide association studies identifies multiple longevity genes
Joris Deelen, Daniel Evans, Dan Arking, Niccolo Tesi, Marianne Nygaard, Xiaomin Liu, Mary Wojczynski, Mary Biggs, Ashley van der Spek, Gil Atzmon, Erin Ware, Chloe Sarnowski, Albert Smith, Ilkka Seppala, Heather Cordell, Janina Dose, Najaf Amin, Alice Arnold, Kristin Ayers, Nir Barzilai, Elizabeth Becker, Marian Beekman, Helene Blanche, Kaare Christensen, Lene Christiansen, Joanna Collerton, Sarah Cubaynes, Steven Cummings, Karen Davies, Birgit Debrabant, Jean-Francois Deleuze, Rachel Duncan, Jessica Faul, Claudio Franceschi, Pilar Galan, Vilmundur Gudnason, Tamara Harris, Martijn Huisman, Mikko Hurme, Carol Jagger, Iris Jansen, Marja Jylha, Mika Kahonen, David Karasik, Sharon Kardia, Andrew Kingston, Thomas Kirkwood, Lenore Launer, Terho Lehtimaki, Wolfgang Lieb, Leo-Pekka Lyytikainen, Carmen Martin-Ruiz, Junxia Min, Almut Nebel, Anne Newman, Chao Nie, Ellen Nohr, Eric Orwoll, Thomas Perls, Michael Province, Bruce Psaty, Olli Raitakari, Marcel Reinders, Jean-Marie Robine, Jerome Rotter, Paola Sebastiani, Jennifer Smith, Thorkild Sorensen, Kent Taylor, Andre Uitterlinden, Wiesje van der Flier, Sven van der Lee, Cornelia van Duijn, Diana van Heemst, James Vaupel, David Weir, Kenny Ye, Yi Zeng, Wanlin Zheng, Henne Holstege, Douglas Kiel, Kathryn Lunetta, P. Slagboom, Joanne Murabito
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) epsilon4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE epsilon2) 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.