| Title | A meta-analysis of genome-wide association studies identifies multiple longevity genes. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | 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, AVernon, Seppälä, I, Cordell, HJ, Dose, J, Amin, N, Arnold, AM, Ayers, KL, Barzilai, N, Becker, EJ, Beekman, M, Blanché, H, Christensen, K, Christiansen, L, Collerton, JC, Cubaynes, S, Cummings, SR, Davies, K, Debrabant, B, Deleuze, J-F, Duncan, R, Faul, J, Franceschi, C, Galan, P, Gudnason, V, Harris, TB, Huisman, M, Hurme, MA, Jagger, C, Jansen, I, Jylhä, M, Kähönen, M, Karasik, D, Kardia, SLR, Kingston, A, Kirkwood, TBL, Launer, LJ, Lehtimäki, T, Lieb, W, Lyytikäinen, 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, JA, Sørensen, TIA, Taylor, KD, Uitterlinden, AG, van der Flier, W, van der Lee, SJ, van Duijn, CM, van Heemst, D, Vaupel, JW, Weir, DR, Ye, K, Zeng, Y, Zheng, W, Holstege, H, Kiel, DP, Lunetta, KL, Slagboom, EP, Murabito, JM |
| Journal | Nature Communications |
| Volume | 10 |
| Issue | 1 |
| Pagination | 3669 |
| Date Published | 08/2019 |
| ISSN Number | 2041-1723 |
| Keywords | genes, Genome-Wide Association Study, GWA, longevity genes, meta-analysis |
| 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. |
| URL | https://www.ncbi.nlm.nih.gov/pubmed/31413261 |
| DOI | 10.1038/s41467-019-11558-2 |
| User Guide Notes | |
| Alternate Journal | Nat Commun |
| Citation Key | 10225 |
| PubMed ID | 31413261 |
| PubMed Central ID | PMC6694136 |
| Grant List | 102858/Z/13/Z / WT_ / Wellcome Trust / United Kingdom MR/J50001X/1 / MRC_ / Medical Research Council / United Kingdom UL1 TR002369 / TR / NCATS NIH HHS / United States G0500997 / MRC_ / Medical Research Council / United Kingdom S10 OD016290 / OD / NIH HHS / United States R01 AG055406 / AG / NIA NIH HHS / United States L60 MD012145 / MD / NIMHD NIH HHS / United States |
