Summary: Genetics may help explain why women are at higher risk for developing chronic pain disorders than men. The study also sheds light on the role the central nervous system plays in the development of chronic pain.
Women may be at greater risk of experiencing chronic pain because the condition has a different genetic basis in men and women.
Keira Johnston of the University of Glasgow and colleagues report these findings in a new study published April 8th in PLOS Genetics.
Chronic pain is a common and potentially debilitating condition that tends to affect more women than men.
To explore this disparity, researchers undertook the largest ever genetic study of chronic pain that analyzed women and men separately. They looked for genetic variants associated with chronic pain in 209,093 women and 178,556 men, and compared the results. In women, 31 genes were associated with chronic pain, while 37 genes were linked in men. A single gene was associated with chronic pain in both sexes.
The researchers also investigated whether the activity of these genes was turned up or down in tissues known to be related to chronic pain.
They found that all 37 genes in men and all but one of the 31 genes in women were active in the dorsal root ganglion, a cluster of nerves in the spinal cord that transmit pain signals from the body to the brain.
The new results support the researchers’ previous work, showing that chronic pain originates to a large extent in the brain, and to a lesser degree in the sites where people may be experiencing pain.
The study also suggests that sex differences in chronic pain likely have at least a partial genetic basis.
They argue that research into chronic pain – and potentially other complex conditions – will likely benefit from approaches that take sex into account.
Overall, these findings add to our understanding of chronic pain and may inform the development of novel therapies for this hard-to-treat condition.
Johnston adds, “Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain.”
About this genetics and pain research news
Source: PLOS Contact: Keira Johnston – PLOS Image: The image is in the public domain
Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank
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.