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

TitleBayesian association scan reveals loci associated with human lifespan and linked biomarkers
Publication TypeJournal Article
Year of Publication2017
AuthorsMcDaid, A, Joshi, PK, Porcu, E, Komljenovic, A, Li, H, Sorrentino, V, Litovchenko, M, Bevers, RPJ, Rüeger, S, Reymond, A, Bochud, M, Deplancke, B, Williams, RW, Robinson-Rechavi, M, Paccaud, F, Rousson, V, Auwerx, J, Wilson, JF, Kutalik, Z
JournalNature Communications
Volume8
Pagination15842
Date Published2017
URLhttp://www.nature.com/doifinder/10.1038/ncomms15842http://www.nature.com/doifinder/10.1038/ncomms15842
DOI10.1038/ncomms15842
Keywords80 and over, Aged, Arylsulfotransferase/genetics, Bayes Theorem, Biomarkers/analysis, Disease/genetics, European Continental Ancestry Group/genetics, Female, Genome-Wide Association Study, Humans, Longevity/genetics, Male, Nerve Tissue Proteins/genetics, Nicotinic/genetics, polymorphism, Receptors, RNA-Binding Proteins/genetics, Single Nucleotide, United Kingdom
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.

WOS ID (UT)

000406360000001

Short TitleNat Comms
Citation Key / SERVAL ID8077
Peer reviewRefereed

                         

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