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- Johnston, KJA (author)
Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank
- Article/chapterEnglish2021
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- 2021-04-08
- Public Library of Science (PLoS),2021
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- LIBRIS-ID:oai:prod.swepub.kib.ki.se:146408886
- http://kipublications.ki.se/Default.aspx?queryparsed=id:146408886URI
- https://doi.org/10.1371/journal.pgen.1009428DOI
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- Language:English
- Summary in:English
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- 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.
Added entries (persons, corporate bodies, meetings, titles ...)
- Ward, J (author)
- Ray, PR (author)
- Adams, MJ (author)
- McIntosh, AM (author)
- Smith, BH (author)
- Strawbridge, RJKarolinska Institutet (author)
- Price, TJ (author)
- Smith, DJ (author)
- Nicholl, BI (author)
- Bailey, MES (author)
- Karolinska Institutet (creator_code:org_t)
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- In:PLoS genetics: Public Library of Science (PLoS)17:4, s. e1009428-1553-7404
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