Joshi, Peter K.Fischer, KristaSchraut, Katharina E.Campbell, HarryEsko, TõnuWilson, James F.2017-07-242016Joshi, Peter K., Krista Fischer, Katharina E. Schraut, Harry Campbell, Tõnu Esko, and James F. Wilson. 2016. “Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan.” Nature Communications 7 (1): 11174. doi:10.1038/ncomms11174. http://dx.doi.org/10.1038/ncomms11174.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33490767Lifespan 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.en-USJournal Article2017-07-2410.1038/ncomms11174