Title | Human longevity: 25 genetic loci associated in 389,166 UK biobank participants |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Pilling, LC, Kuo, C-L, Sicinski, K, Tamosauskaite, J, Kuchel, GA, Harries, LW, Herd, P, Wallace, RB, Ferrucci, L, Melzer, D |
Journal | Aging |
Volume | 9 |
Issue | 12 |
Pagination | 2504-2520 |
Keywords | Cross-National, Genetics, Genome, GWAS, Longevity |
Abstract | We undertook a genome-wide association study (GWAS) of parental longevity in European descent UK Biobank participants. For combined mothers' and fathers' attained age, 10 loci were associated (p<5*10(-8)), including 8 previously identified for traits including survival, Alzheimer's and cardiovascular disease. Of these, 4 were also associated with longest 10% survival (mother's age >= 90 years, father's >= 87 years), with 2 additional associations including MC2R intronic variants (coding for the adrenocorticotropic hormone receptor). Mother's age at death was associated with 3 additional loci (2 linked to autoimmune conditions), and 8 for fathers only. An attained age genetic risk score associated with parental survival in the US Health and Retirement Study and the Wisconsin Longitudinal Study and with having a centenarian parent (n=1,181) in UK Biobank. The results suggest that human longevity is highly polygenic with prominent roles for loci likely involved in cellular senescence and inflammation, plus lipid metabolism and cardiovascular conditions. There may also be gender specific routes to longevity. |
URL | http://www.aging-us.com/article/101334/texthttp://www.aging-us.com/article/101334/text?_escaped_fragment_= |
DOI | 10.18632/aging.101334 |
Short Title | aging |
Citation Key | 9442 |
PubMed ID | 29227965 |
PubMed Central ID | PMC5764389 |
Grant List | U01 AG009740 / AG / NIA NIH HHS / United States MC_QA137853 / / Medical Research Council / United Kingdom P01 AG021079 / AG / NIA NIH HHS / United States R01 AG033285 / AG / NIA NIH HHS / United States P30 AG017266 / AG / NIA NIH HHS / United States MR/M023095/1 / / Medical Research Council / United Kingdom R01 AG009775 / AG / NIA NIH HHS / United States |