Genome-wide association study of multisite chronic pain in UK Biobank

Johnston, K. J.A., Adams, M. J., Nicholl, B. I. , Ward, J., Strawbridge, R. , Ferguson, A., McIntosh, A., Bailey, M. E.S. and Smith, D. J. (2019) Genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genetics, 15(6), e1008164. (doi:10.1371/journal.pgen.1008164) (PMID:31194737) (PMCID:PMC6592570)

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Abstract

Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ‘chronic pain grade’, have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.

Item Type:Articles
Additional Information:We thank all participants in the UK Biobank study. UK Biobank was established by the Wellcome Trust, Medical Research Council, Department of Health, Scottish Government and Northwest Regional Development Agency. UK Biobank has also had funding from the Welsh Assembly Government and the British Heart Foundation. Data collection was funded by UK Biobank.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ferguson, Amy and Ward, Mr Joey and Johnston, Ms Keira and Smith, Professor Daniel and Bailey, Dr Mark and Nicholl, Dr Barbara and Strawbridge, Dr Rona
Authors: Johnston, K. J.A., Adams, M. J., Nicholl, B. I., Ward, J., Strawbridge, R., Ferguson, A., McIntosh, A., Bailey, M. E.S., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:PLoS Genetics
Publisher:Public Library of Science
ISSN:1553-7390
ISSN (Online):1553-7404
Published Online:13 June 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in PLoS Genetics 15(6):e1008164
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
3021310Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health
632341MRC Doctoral Training Grant 2013/14, 2014/15 and 2015/16George BaillieMedical Research Council (MRC)MR/K501335/1MVLS GRADUATE SCHOOL
3029570Mental Health Data PathfinderDaniel SmithMedical Research Council (MRC)MC_PC_17217HW - Mental Health and Wellbeing