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

Aaron F. McDaid, Peter K. Joshi, Eleonora Porcu, Andrea Komljenovic, Hao Li, Vincenzo Sorrentino, Maria Litovchenko, Roel P. J. Bevers, Sina Rüeger, Alexandre Reymond, Murielle Bochud, Bart Deplancke, Robert W. Williams, Marc Robinson-Rechavi, Fred Paccaud, Valentin Rousson, Johan Auwerx, James F. Wilson and Zoltán Kutalik ()
Additional contact information
Aaron F. McDaid: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
Peter K. Joshi: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh
Eleonora Porcu: Swiss Institute of Bioinformatics
Andrea Komljenovic: Swiss Institute of Bioinformatics
Hao Li: Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL)
Vincenzo Sorrentino: Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL)
Maria Litovchenko: Swiss Institute of Bioinformatics
Roel P. J. Bevers: Swiss Institute of Bioinformatics
Sina Rüeger: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
Alexandre Reymond: Center for Integrative Genomics, University of Lausanne
Murielle Bochud: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
Bart Deplancke: Swiss Institute of Bioinformatics
Robert W. Williams: Genomics and Informatics, University of Tennessee Health Science Center
Marc Robinson-Rechavi: Swiss Institute of Bioinformatics
Fred Paccaud: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
Valentin Rousson: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
Johan Auwerx: Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL)
James F. Wilson: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh
Zoltán Kutalik: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15842

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