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

Détails

Ressource 1Télécharger: ncomms15842.pdf (870.18 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_C06E0694F6CC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Bayesian association scan reveals loci associated with human lifespan and linked biomarkers.
Périodique
Nature communications
Auteur(s)
McDaid A.F., Joshi P.K., Porcu E., Komljenovic A., Li H., Sorrentino V., Litovchenko M., Bevers RPJ, Rüeger S., Reymond A., Bochud M., Deplancke B., Williams R.W., Robinson-Rechavi M., Paccaud F., Rousson V., Auwerx J., Wilson J.F., Kutalik Z.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
27/07/2017
Peer-reviewed
Oui
Volume
8
Pages
15842
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
Aged, Aged, 80 and over, 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, Polymorphism, Single Nucleotide, RNA-Binding Proteins/genetics, Receptors, Nicotinic/genetics, United Kingdom
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/07/2017 15:53
Dernière modification de la notice
09/05/2019 0:42
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