In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 17, No. 4 ( 2021-4-8), p. e1009428-
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 r g 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.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009428
DOI:
10.1371/journal.pgen.1009428.g001
DOI:
10.1371/journal.pgen.1009428.g002
DOI:
10.1371/journal.pgen.1009428.g003
DOI:
10.1371/journal.pgen.1009428.g004
DOI:
10.1371/journal.pgen.1009428.g005
DOI:
10.1371/journal.pgen.1009428.t001
DOI:
10.1371/journal.pgen.1009428.t002
DOI:
10.1371/journal.pgen.1009428.t003
DOI:
10.1371/journal.pgen.1009428.t004
DOI:
10.1371/journal.pgen.1009428.t005
DOI:
10.1371/journal.pgen.1009428.s001
DOI:
10.1371/journal.pgen.1009428.s002
DOI:
10.1371/journal.pgen.1009428.s003
DOI:
10.1371/journal.pgen.1009428.s004
DOI:
10.1371/journal.pgen.1009428.s005
DOI:
10.1371/journal.pgen.1009428.s006
DOI:
10.1371/journal.pgen.1009428.s007
DOI:
10.1371/journal.pgen.1009428.s008
DOI:
10.1371/journal.pgen.1009428.s009
DOI:
10.1371/journal.pgen.1009428.s010
DOI:
10.1371/journal.pgen.1009428.s011
DOI:
10.1371/journal.pgen.1009428.s012
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2186725-2
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