Human longevity: 25 genetic loci associated in 389,166 UK biobank participants

TitleHuman longevity: 25 genetic loci associated in 389,166 UK biobank participants
Publication TypeJournal Article
Year of Publication2017
AuthorsPilling, LC, Kuo, C-L, Sicinski, K, Tamosauskaite, J, Kuchel, GA, Harries, LW, Herd, P, Wallace, RB, Ferrucci, L, Melzer, D
JournalAging
Volume9
Issue12
Pagination2504-2520
KeywordsCross-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.

URLhttp://www.aging-us.com/article/101334/texthttp://www.aging-us.com/article/101334/text?_escaped_fragment_=
DOI10.18632/aging.101334
Short Titleaging
Citation Key9442
PubMed ID29227965
PubMed Central IDPMC5764389
Grant ListU01 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