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 Ruëger, Alexandre Reymond, Murielle Bochud, Bart Deplancke, Robert Williams, Marc Robinson-Rechavi, Fred Paccaud, Valentin Rousson, Johan Auwerx, James F. Wilson, Zoltán Kutalik

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Article number15842
JournalNature Communications
Volume8
DOIs
StatePublished - Jul 27 2017

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biomarkers
Biomarkers
loci
Association reactions
Single Nucleotide Polymorphism
Parental Death
Gene expression
HapMap Project
Brain
Caloric Restriction
Genes
gene expression
Genome-Wide Association Study
Random Allocation
organisms
death
genes
brain
constrictions
Parents

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

McDaid, A. F., Joshi, P. K., Porcu, E., Komljenovic, A., Li, H., Sorrentino, V., ... Kutalik, Z. (2017). Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. Nature Communications, 8, [15842]. https://doi.org/10.1038/ncomms15842

Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. / McDaid, Aaron F.; Joshi, Peter K.; Porcu, Eleonora; Komljenovic, Andrea; Li, Hao; Sorrentino, Vincenzo; Litovchenko, Maria; Bevers, Roel P.J.; Ruëger, Sina; Reymond, Alexandre; Bochud, Murielle; Deplancke, Bart; Williams, Robert; Robinson-Rechavi, Marc; Paccaud, Fred; Rousson, Valentin; Auwerx, Johan; Wilson, James F.; Kutalik, Zoltán.

In: Nature Communications, Vol. 8, 15842, 27.07.2017.

Research output: Contribution to journalArticle

McDaid, AF, Joshi, PK, Porcu, E, Komljenovic, A, Li, H, Sorrentino, V, Litovchenko, M, Bevers, RPJ, Ruëger, S, Reymond, A, Bochud, M, Deplancke, B, Williams, R, Robinson-Rechavi, M, Paccaud, F, Rousson, V, Auwerx, J, Wilson, JF & Kutalik, Z 2017, 'Bayesian association scan reveals loci associated with human lifespan and linked biomarkers', Nature Communications, vol. 8, 15842. https://doi.org/10.1038/ncomms15842
McDaid, Aaron F. ; Joshi, Peter K. ; Porcu, Eleonora ; Komljenovic, Andrea ; Li, Hao ; Sorrentino, Vincenzo ; Litovchenko, Maria ; Bevers, Roel P.J. ; Ruëger, Sina ; Reymond, Alexandre ; Bochud, Murielle ; Deplancke, Bart ; Williams, Robert ; Robinson-Rechavi, Marc ; Paccaud, Fred ; Rousson, Valentin ; Auwerx, Johan ; Wilson, James F. ; Kutalik, Zoltán. / Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. In: Nature Communications. 2017 ; Vol. 8.
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