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Research Paper|Volume 9, Issue 12|pp 2504—2520

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

Luke C. Pilling1, Chia-Ling Kuo2, Kamil Sicinski3, Jone Tamosauskaite1, George A. Kuchel4, Lorna W. Harries5, Pamela Herd6, Robert Wallace7, Luigi Ferrucci8, David Melzer1,4
  • 1Epidemiology and Public Health Group, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Exeter, EX2 5DW, UK
  • 2Department 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
  • 3Center for Demography of Health and Aging, University of Wisconsin, Madison, WI 53706, USA
  • 4UConn Center on Aging, University of Connecticut, Farmington, CT 06030, USA
  • 5Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Exeter, UK
  • 6La Follette School of Public Affairs and the Department of Sociology, University of Wisconsin, Madison, WI 53706, USA
  • 7College of Public Health, University of Iowa, Iowa City, IA 52242, USA
  • 8National Institute on Aging, Baltimore, MD 21224, USA
Received: September 26, 2017Accepted: November 26, 2017Published: December 6, 2017
https://doi.org/10.18632/aging.101334

Copyright: © 2017 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.

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 (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.