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Nat Commun. 2017 Jul 27;8:15842. doi: 10.1038/ncomms15842.

Bayesian association scan reveals loci associated with human lifespan and linked biomarkers.

Author information

1
Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
2
Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
3
Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland.
4
Center for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland.
5
Department of Ecology and Evolution, University of Lausanne, Lausanne 1015, Switzerland.
6
Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
7
Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
8
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
9
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland.

Abstract

The enormous variation in human lifespan is in part due to a myriad of sequence variants, only a few of which have been revealed to date. Since many life-shortening events are related to diseases, we developed a Mendelian randomization-based method combining 58 disease-related GWA studies to derive longevity priors for all HapMap SNPs. A Bayesian association scan, informed by these priors, for parental age of death in the UK Biobank study (n=116,279) revealed 16 independent SNPs with significant Bayes factor at a 5% false discovery rate (FDR). Eleven of them replicate (5% FDR) in five independent longevity studies combined; all but three are depleted of the life-shortening alleles in older Biobank participants. Further analysis revealed that brain expression levels of nearby genes (RBM6, SULT1A1 and CHRNA5) might be causally implicated in longevity. Gene expression and caloric restriction experiments in model organisms confirm the conserved role for RBM6 and SULT1A1 in modulating lifespan.

PMID:
28748955
PMCID:
PMC5537485
DOI:
10.1038/ncomms15842
[Indexed for MEDLINE]
Free PMC Article

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