Research Paper Volume 9, Issue 12 pp 2504—2520
Human longevity: 25 genetic loci associated in 389,166 UK biobank participants
- 1 Epidemiology and Public Health Group, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Exeter, EX2 5DW, UK
- 2 Department of Community Medicine and Health Care, Connecticut Institute for Clinical and Translational Science, Institute for Systems Genomics, University of Connecticut Health Center, CT 06269, USA
- 3 Center for Demography of Health and Aging, University of Wisconsin, Madison, WI 53706, USA
- 4 UConn Center on Aging, University of Connecticut, Farmington, CT 06030, USA
- 5 Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Exeter, UK
- 6 La Follette School of Public Affairs and the Department of Sociology, University of Wisconsin, Madison, WI 53706, USA
- 7 College of Public Health, University of Iowa, Iowa City, IA 52242, USA
- 8 National Institute on Aging, Baltimore, MD 21224, USA
received: September 26, 2017 ; accepted: November 26, 2017 ; published: December 6, 2017 ;https://doi.org/10.18632/aging.101334
How to Cite
Copyright: Pilling et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 (mothers age ≥90 years, fathers ≥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.