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

Author

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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
    Centre for Cardiovascular Sciences, Queen’s Medical Research Institute, University of Edinburgh, Royal Infirmary of Edinburgh, Little France Crescent)

  • 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
    Boston Children's Hospital
    Program in Medical and Population Genetics, Broad Institute
    Harvard Medical School)

  • James F. Wilson

    (Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital)

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.

Suggested Citation

  • Peter K. Joshi & Krista Fischer & Katharina E. Schraut & Harry Campbell & Tõnu Esko & James F. Wilson, 2016. "Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan," Nature Communications, Nature, vol. 7(1), pages 1-7, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11174
    DOI: 10.1038/ncomms11174
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    Cited by:

    1. Hakhamanesh Mostafavi & Tomaz Berisa & Felix R Day & John R B Perry & Molly Przeworski & Joseph K Pickrell, 2017. "Identifying genetic variants that affect viability in large cohorts," PLOS Biology, Public Library of Science, vol. 15(9), pages 1-29, September.

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