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 and James F. Wilson ()
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Peter K. Joshi: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh
Krista Fischer: Estonian Genome Center, University of Tartu
Katharina E. Schraut: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh
Harry Campbell: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh
Tõnu Esko: Estonian Genome Center, University of Tartu
James F. Wilson: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11174

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