Clinical study|Articles in Press

Genotype-by-environment interactions in chronic back pain

  • Ivan A. Kuznetsov
    Center of Life Sciences, Skolkovo Institute of Science and Technology, 30 bld.1 Bolshoy Boulevard, Moscow 121205, Russia
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  • Yakov A. Tsepilov
    Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, 10 Lavrentiev Ave, Novosibirsk, 630090, Russia

    Laboratory of Theoretical and Applied Functional Genomics, Novosibirsk State University, 1 Pirogova St, Novosibirsk, 630090, Russia

    Kurchatov genomics center of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentiev Ave, Novosibirsk, 630090, Russia
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  • Maxim B. Freidin
    Department of Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, Mile End Rd, Bethnal Green, London E1 4DQ, UK
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  • Frances M.K. Williams
    Department of Twin Research and Genetic Epidemiology, King's College London, Westminster Bridge Rd, London SE1 7EH, UK
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  • Author Footnotes
    § These authors contributed equally.
    Pradeep Suri
    § These authors contributed equally.
    Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, 1660 S. Columbian Way, Seattle, WA 98108, USA

    Division of Rehabilitation Care Services, 1660 S. Columbian Way, Seattle, WA 98108, USA

    Clinical Learning, Evidence, and Research Center, University of Washington, 325 Ninth AvBox 359612, Seattle, WA 98104, USA
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  • Author Footnotes
    § These authors contributed equally.
    Yurii S. Aulchenko
    Corresponding author: PolyOmica, Het Vlaggeschip 61, 's-Hertogenbosch, PA 5237, The Netherlands. Tel.: +7 (383) 363-49-80; fax:+7 (383) 333-12-78.
    § These authors contributed equally.
    Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics, 10 Lavrentiev Ave, Novosibirsk, 630090, Russia

    PolyOmica, Het Vlaggeschip 61, ‘s-Hertogenbosch, PA 5237, The Netherlands
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  • Author Footnotes
    § These authors contributed equally.



      Chronic back pain (CBP) is a common debilitating condition with substantial societal impact. While understanding genotype-by-environment (GxE) interactions may be crucial to achieving the goals of personalized medicine, there are few large-scale studies investigating this topic for CBP. None of them systematically explore multiple CBP risk factors.


      To estimate the extent to which genetic effects on CBP are modified by known demographic and clinical risk factors.


      Case-control study, genome-wide GxE interaction study.


      Data on up to 331,610 unrelated participants (57,881 CBP cases and 273,729 controls) from the UK Biobank cohort were used. UK Biobank is a prospective cohort with collected deep genetic and phenotypic data on approximately 500,000 individuals across the UK.


      Self-reported chronic back pain.


      We applied a whole-genome approach to estimate the proportion of phenotypic variance explained by interactions between genotype and 12 known risk factors. We also analyzed if effects of common single-nucleotide polymorphisms on CBP are changed in presence of known risk factors.


      The results indicate a modest, if any, modification of genetic effects by examined risk factors in CBP. Our estimates suggest that detecting such weak effects would require a sample size of millions of individuals.


      The GxE interactions with examined common risk factors for CBP are either weak or absent. Interactions of such magnitude are unlikely to have the potential to inform and influence treatment strategies. Risk estimation models may use common genetic variation and the considered risk factors as independent predictors, without accounting for GxE.


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