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

Author

Listed:
  • Aaron F. McDaid

    (Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • 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
    Center for Integrative Genomics, University of Lausanne)

  • Andrea Komljenovic

    (Swiss Institute of Bioinformatics
    University of Lausanne)

  • 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
    Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics)

  • Roel P. J. Bevers

    (Swiss Institute of Bioinformatics
    Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics)

  • Sina Rüeger

    (Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • 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
    Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics)

  • Robert W. Williams

    (Genomics and Informatics, University of Tennessee Health Science Center)

  • Marc Robinson-Rechavi

    (Swiss Institute of Bioinformatics
    University of Lausanne)

  • 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
    MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital)

  • Zoltán Kutalik

    (Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital
    Swiss Institute of Bioinformatics)

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.

Suggested Citation

  • 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, 2017. "Bayesian association scan reveals loci associated with human lifespan and linked biomarkers," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15842
    DOI: 10.1038/ncomms15842
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    Cited by:

    1. Karlsson Linnér, Richard & Koellinger, Philipp D., 2022. "Genetic risk scores in life insurance underwriting," Journal of Health Economics, Elsevier, vol. 81(C).

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