Bayesian association scan reveals loci associated with human lifespan and linked biomarkers.
- McDaid AF Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
- Joshi PK Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland.
- Porcu E Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
- Komljenovic A Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
- Li H Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
- Sorrentino V Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
- Litovchenko M Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
- Bevers RPJ Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
- Rüeger S Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
- Reymond A Center for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland.
- Bochud M Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
- Deplancke B Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
- Williams RW Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
- Robinson-Rechavi M Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
- Paccaud F Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
- Rousson V Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
- Auwerx J Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
- Wilson JF Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland.
- Kutalik Z Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne 1010, Switzerland.
- 2017-07-28
Published in:
- Nature communications. - 2017
Aged
Aged, 80 and over
Arylsulfotransferase
Bayes Theorem
Biomarkers
Disease
European Continental Ancestry Group
Female
Genome-Wide Association Study
Humans
Longevity
Male
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
RNA-Binding Proteins
Receptors, Nicotinic
United Kingdom
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/ncomms15842
- PMID 28748955
- Persistent URL
- https://folia.unifr.ch/global/documents/25238
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