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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.

Author information

1
Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland.
2
Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia.
3
Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh EH16 4TJ, Scotland.
4
Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Cambridge, Massachusetts 02141, USA.
5
Program in Medical and Population Genetics, Broad Institute, Cambridge Center 7, Cambridge, Massachusetts 02242, USA.
6
Department of Genetics, Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA.
7
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland.

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.

PMID:
27029810
PMCID:
PMC5438072
DOI:
10.1038/ncomms11174
[Indexed for MEDLINE]
Free PMC Article

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