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

Peter K Joshi, Krista Fischer, Katharina E Schraut, Harry Campbell, Tõnu Esko, James F Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number11174
Number of pages7
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 31 Mar 2016

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