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

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

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Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland.
Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh EH16 4TJ, Scotland.
Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Cambridge, Massachusetts 02141, USA.
Program in Medical and Population Genetics, Broad Institute, Cambridge Center 7, Cambridge, Massachusetts 02242, USA.
Department of Genetics, Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland.


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.

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