| Title: | Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank |
| Journal: | PLOS Genetics |
| Published: | 8 Apr 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33830993/ |
| DOI: | https://doi.org/10.1371/journal.pgen.1009428 |
| URL: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009428&type=printable |
| Citations: | 49 (29 in last 2 years) as of 8 Aug 2024 |
Publication 5735
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Abstract
Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.11 Authors
- Keira J. A. Johnston
- Joey Ward
- Pradipta R. Ray
- Mark J. Adams
- Andrew M. McIntosh
- Blair H. Smith
- Rona J. Strawbridge
- Theodore J. Price
- Daniel J. Smith
- Barbara I. Nicholl
- Mark E. S. Bailey
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