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Aging (Albany NY). 2016 Mar;8(3):547-60.

Human longevity is influenced by many genetic variants: evidence from 75,000 UK Biobank participants.

Author information

1
Epidemiology and Public Health Group, University of Exeter Medical School, RILD Level 3, Royal Devon and Exeter Hospital, Exeter, EX2 5DW, UK.
2
Genetics of Complex Traits Group, University of Exeter Medical School, RILD Level 3, Royal Devon and Exeter Hospital, Exeter, EX2 5DW, UK.
3
School of Public Health, Department of Biostatistics, Boston University, Boston, MA 02215, USA.
4
The Framingham Heart Study, Framingham, MA 01702, USA.
5
Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
6
Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, RILD Level 3, Royal Devon and Exeter Hospital, Exeter, EX2 5DW, UK.
7
Institut National de la Santé et de la Recherche Médicale (INSERM U1198), 34394 Montpellier, France.
8
Ecole Pratique des Hautes études (EPHE), 75014 Paris, France.
9
Cambridge Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SR, UK.
10
Center on Aging, University of Connecticut, Farmington, CT 06030, USA.
11
National Institute on Aging, Baltimore, MD 21224, USA.

Abstract

Variation in human lifespan is 20 to 30% heritable in twins but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father's and/or mother's data, excluding early deaths). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested. In GWAS, a nicotine receptor locus(CHRNA3, previously associated with increased smoking and lung cancer) was associated with fathers' survival. Less common variants requiring further confirmation were also identified. Offspring of longer lived parents had more protective alleles for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer's disease. In candidate analyses, variants in the TOMM40/APOE locus were associated with longevity, but FOXO variants were not. Associations between extreme longevity (mother >=98 years, fathers >=95 years, n=1,339) and disease alleles were similar, with an additional association with HDL cholesterol (p=5.7x10-3). These results support a multiple protective factors model influencing lifespan and longevity (top 1% survival) in humans, with prominent roles for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable.

KEYWORDS:

GWAS; aging; genetic; human; longevity

PMID:
27015805
PMCID:
PMC4833145
DOI:
10.18632/aging.100930
[Indexed for MEDLINE]
Free PMC Article

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