Human Longevity: 25 Genetic Loci Associated in 389,166 UK Biobank Participants

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2017 Dec 12

PMID 29227965

Citations 105

Authors

Luke C Pilling

Chia-Ling Kuo

Kamil Sicinski

Jone Tamosauskaite

George A Kuchel

Lorna W Harries

Pamela Herd

Robert Wallace

Luigi Ferrucci

David Melzer

Affiliations

Soon will be listed here.

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), 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 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 (=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.

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