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

Nat Commun. 2016 Mar 31:7:11174. doi: 10.1038/ncomms11174.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / physiology
  • Cohort Studies
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Longevity / genetics*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Proportional Hazards Models
  • Receptors, Nicotinic / genetics*
  • Receptors, Nicotinic / physiology
  • Sex Factors
  • United Kingdom


  • Apolipoproteins E
  • CHRNA5 protein, human
  • Nerve Tissue Proteins
  • Receptors, Nicotinic
  • nicotinic receptor subunit alpha3