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

Luke C Pilling; Chia-Ling Kuo; Kamil Sicinski; Jone Tamosauskaite; George A Kuchel; Lorna W Harries; Pamela Herd; Robert Wallace; Luigi Ferrucci; David Melzer

doi:10.18632/aging.101334

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

Journal article

Open access

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

Luke C Pilling, Chia-Ling Kuo, Kamil Sicinski, Jone Tamosauskaite, George A Kuchel, Lorna W Harries, Pamela Herd, Robert Wallace, Luigi Ferrucci and David Melzer

Aging (Albany, NY.), Vol.9(12), pp.2504-2520

12/06/2017

DOI: 10.18632/aging.101334

PMCID: PMC5764389

PMID: 29227965

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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.

Adult

Aged

Biological Specimen Banks

Female

Genome-Wide Association Study

Humans

Longevity - genetics

Male

Middle Aged

Multifactorial Inheritance

Parents

United Kingdom

Details

Title: Subtitle: Human longevity: 25 genetic loci associated in 389,166 UK biobank participants
Creators: Luke C Pilling - Royal Devon and Exeter Hospital
Chia-Ling Kuo - UConn Health
Kamil Sicinski - University of Wisconsin–Madison
Jone Tamosauskaite - Royal Devon and Exeter Hospital
George A Kuchel - UConn Health
Lorna W Harries - University of Exeter
Pamela Herd - University of Wisconsin–Madison
Robert Wallace - University of Iowa
Luigi Ferrucci - National Institute on Aging
David Melzer - Royal Devon and Exeter Hospital
Resource Type: Journal article
Publication Details: Aging (Albany, NY.), Vol.9(12), pp.2504-2520
DOI: 10.18632/aging.101334
PMID: 29227965
PMCID: PMC5764389
NLM abbreviation: Aging (Albany NY)
ISSN: 1945-4589
eISSN: 1945-4589
Grant note: U01 AG009740 / NIA NIH HHS MR/M023095/1 / Medical Research Council P30 AG017266 / NIA NIH HHS R01 AG009775 / NIA NIH HHS P01 AG021079 / NIA NIH HHS R01 AG033285 / NIA NIH HHS MC_QA137853 / Medical Research Council
Language: English
Date published: 12/06/2017
Academic Unit: Epidemiology; Injury Prevention Research Center; Internal Medicine
Record Identifier: 9984363634802771

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