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

A F McDaid; Peter Joshi; E. Porcu; A Komljenovic; H. Li; V Sorrentino; M Litovchenko; R Bevers; Sina Rüeger; Alexandre Reymond; Murielle Bochud; Bart Deplancke; R. Williams; M. Robinson-Rechavi; Fred Paccaud; Valentin Rousson; Johan Auwerx; James Wilson; Zoltan Kutalik

doi:10.1038/ncomms15842

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

A F McDaid, Peter Joshi, E. Porcu, A Komljenovic, H. Li, V Sorrentino, M Litovchenko, R Bevers, Sina Rüeger, Alexandre Reymond, Murielle Bochud, Bart Deplancke, R. Williams, M. Robinson-Rechavi, Fred Paccaud, Valentin Rousson, Johan Auwerx, James Wilson, Zoltan Kutalik

Research output: Contribution to journal › Article › peer-review

Abstract

The enormous variations in human lifespan are 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, 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 language	English
Journal	Nature Communications
DOIs	https://doi.org/10.1038/ncomms15842
Publication status	Published - 27 Jul 2017

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McDaid, A. F., Joshi, P., Porcu, E., Komljenovic, A., Li, H., Sorrentino, V., Litovchenko, M., Bevers, R., Rüeger, S., Reymond, A., Bochud, M., Deplancke, B., Williams, R., Robinson-Rechavi, M., Paccaud, F., Rousson, V., Auwerx, J., Wilson, J., & Kutalik, Z. (2017). Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. Nature Communications. https://doi.org/10.1038/ncomms15842

McDaid, A F ; Joshi, Peter ; Porcu, E. ; Komljenovic, A ; Li, H. ; Sorrentino, V ; Litovchenko, M ; Bevers, R ; Rüeger, Sina ; Reymond, Alexandre ; Bochud, Murielle ; Deplancke, Bart ; Williams, R. ; Robinson-Rechavi, M. ; Paccaud, Fred ; Rousson, Valentin ; Auwerx, Johan ; Wilson, James ; Kutalik, Zoltan. / Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. In: Nature Communications. 2017.

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title = "Bayesian association scan reveals loci associated with human lifespan and linked biomarkers",

abstract = "The enormous variations in human lifespan are 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, 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. ",

author = "McDaid, {A F} and Peter Joshi and E. Porcu and A Komljenovic and H. Li and V Sorrentino and M Litovchenko and R Bevers and Sina R{\"u}eger and Alexandre Reymond and Murielle Bochud and Bart Deplancke and R. Williams and M. Robinson-Rechavi and Fred Paccaud and Valentin Rousson and Johan Auwerx and James Wilson and Zoltan Kutalik",

year = "2017",

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McDaid, AF, Joshi, P, Porcu, E, Komljenovic, A, Li, H, Sorrentino, V, Litovchenko, M, Bevers, R, Rüeger, S, Reymond, A, Bochud, M, Deplancke, B, Williams, R, Robinson-Rechavi, M, Paccaud, F, Rousson, V, Auwerx, J, Wilson, J & Kutalik, Z 2017, 'Bayesian association scan reveals loci associated with human lifespan and linked biomarkers', Nature Communications. https://doi.org/10.1038/ncomms15842

Bayesian association scan reveals loci associated with human lifespan and linked biomarkers. / McDaid, A F; Joshi, Peter; Porcu, E.; Komljenovic, A; Li, H.; Sorrentino, V; Litovchenko, M; Bevers, R; Rüeger, Sina; Reymond, Alexandre; Bochud, Murielle; Deplancke, Bart; Williams, R.; Robinson-Rechavi, M.; Paccaud, Fred; Rousson, Valentin; Auwerx, Johan; Wilson, James; Kutalik, Zoltan.

In: Nature Communications, 27.07.2017.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Bayesian association scan reveals loci associated with human lifespan and linked biomarkers

AU - McDaid, A F

AU - Joshi, Peter

AU - Porcu, E.

AU - Komljenovic, A

AU - Li, H.

AU - Sorrentino, V

AU - Litovchenko, M

AU - Bevers, R

AU - Rüeger, Sina

AU - Reymond, Alexandre

AU - Bochud, Murielle

AU - Deplancke, Bart

AU - Williams, R.

AU - Robinson-Rechavi, M.

AU - Paccaud, Fred

AU - Rousson, Valentin

AU - Auwerx, Johan

AU - Wilson, James

AU - Kutalik, Zoltan

PY - 2017/7/27

Y1 - 2017/7/27

N2 - The enormous variations in human lifespan are 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, 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.

AB - The enormous variations in human lifespan are 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, 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.

U2 - 10.1038/ncomms15842

DO - 10.1038/ncomms15842

M3 - Article

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -

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

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