Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan

Lifespan is a trait of enormous personal interest. Research into the biological basis of human lifespan, however, is hampered by the long time to death. Using a novel approach of regressing (272,081) parental lifespans beyond age 40 years on participant genotype in a new large data set (UK Biobank),...

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Published in:Nature communications Vol. 7; no. 1; pp. 11174 - 7
Main Authors: Joshi, Peter K., Fischer, Krista, Schraut, Katharina E., Campbell, Harry, Esko, Tõnu, Wilson, James F.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 31.03.2016
Nature Publishing Group
Nature Portfolio
Subjects:
631/208/726/649
631/443/7
Adult
Age Factors
Aged
Aged, 80 and over
Apolipoproteins E - genetics
Apolipoproteins E - physiology
Cohort Studies
Female
Genome-Wide Association Study
Genotype
Humanities and Social Sciences
Humans
Life span
Longevity - genetics
Male
Middle Aged
multidisciplinary
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - physiology
Proportional Hazards Models
Receptors, Nicotinic - genetics
Receptors, Nicotinic - physiology
Science
Science (multidisciplinary)
Sex Factors
United Kingdom
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Lifespan is a trait of enormous personal interest. Research into the biological basis of human lifespan, however, is hampered by the long time to death. Using a novel approach of regressing (272,081) parental lifespans beyond age 40 years on participant genotype in a new large data set (UK Biobank), we here show that common variants near the apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 genes are associated with lifespan. The effects are strongly sex and age dependent, with APOE ɛ4 differentially influencing maternal lifespan ( P =4.2 × 10 −15 , effect −1.24 years of maternal life per imputed risk allele in parent; sex difference, P =0.011), and a locus near CHRNA3/5 differentially affecting paternal lifespan ( P =4.8 × 10 −11 , effect −0.86 years per allele; sex difference P =0.075). Rare homozygous carriers of the risk alleles at both loci are predicted to have 3.3–3.7 years shorter lives. Understanding the genetic influences on human aging requires a large number of subjects for a study of sufficient power. Here, Jim Wilson and colleagues use information on parental ages at death to show that common variants near the genes for apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 are associated with longer lifespan.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms11174