Different Pain, Same Genes?
Different chronic pain syndromes share genetic risk factors, according to a study published online May 29 in Pain. The study, led by Frances Williams of King’s College London, UK, studied twins to parse the genetic and environmental contributors to these conditions. The researchers found that chronic widespread pain (CWP), chronic pelvic pain (CPP), irritable bowel syndrome (IBS), and dry eye disease were more likely to co-occur than expected by chance. This was best explained by a shared predisposing factor for these different disorders, and 66 percent of the shared vulnerability could be explained by genes.
“This is important because it gives us the sense that there is something to go after genetically,” Williams told PRF. “It won’t be one gene; it’ll be lots and lots of genes that probably act centrally in the brain rather than peripherally.”
Though genetic studies on CWP alone have begun to reveal risk variants (Peters et al., 2013), the ones that increase risk for all of these disorders could be found by combining people with different chronic pain conditions in a genomewide association study (GWAS), which works best with large sample sizes. A similar approach has uncovered genetic overlaps between different psychiatric disorders (Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013).
The new study suggests that such a combinatorial approach could be a good one for chronic pain.
“Because we’ve shown a relationship between four of these conditions, we could potentially put all of them together in one GWAS pot and get an adequate sample size to find variants that predispose to pain,” Williams said. “This might reveal new pathways for pain that we don’t know about and thereby identify new targets for treatment.”
Chronic pain syndromes comprise collections of diffuse symptoms that have no apparent pathology to explain the pain. Symptoms such as fatigue and headache also overlap between the conditions, and an individual diagnosed with one syndrome often shows signs of another (see PRF related news story). Clustering of the disorders in the same people suggests they stem from the same underlying problems. Whether these reflect genetic or environmental influences can be addressed by twin studies.
“I think this is a really interesting study that helps us start thinking about mechanisms,” said Nancy Pedersen, who conducts twin studies to understand the etiology of chronic diseases and aging at the Karolinska Institute, Stockholm, Sweden. Pedersen was not involved in the study.
“Here, they show there’s a lot of overlap in the genetic influences important for these syndromes,” Pedersen added. “Of course, there will still be disorder-specific genetic influences, but here we see that the common one is substantial.”
Pedersen and colleagues have done a similar study using the Swedish twin registry to analyze the co-occurrence of four syndromes, including CWP and IBS, and depression and anxiety (Kato et al., 2009).
Female factor
Comparing a disorder’s occurrence in monozygotic twins, who are genetically identical and share the same environment, to that in dizygotic twins, who share 50 percent of their genes and the same environment, helps isolate the amount of risk due to genetic versus environmental factors. A greater concordance among monozygotic twins, for example, argues that a genetic factor is at work.
The new study took this approach, looking at the occurrence of five different disorders—CWP, IBS, CPP, dry eye disease, and migraine—in 8,564 twins from the TwinsUK collection. Monozygotic twins showed a higher concordance for each condition, and heritability ranged from 19 to 46 percent for each disorder.
The researchers then tallied how often the different disorders co-occurred in the same person. Migraine was not found to co-occur with another chronic pain disorder at a rate greater than expected by chance, suggesting that it did not belong in the same category as the other four conditions. Thus, it was dropped from further analysis.
But significant correlations were found between pairings of the other four disorders, and these were higher for monozygotic twins, indicating a genetic influence on the development of both conditions. Because the twin sample was enriched for females, and because one of the disorders—chronic pelvic pain—occurs only in women, the researchers modeled the data from women only. The model revealed that a common predisposing factor could best explain the co-occurrence of the chronic pain conditions.
This chronic pain predisposition showed a strong genetic influence (66 percent ) and a smaller environmental influence (34 percent) unique to each person. This chronic pain predisposition contributed more to risk for CWP and IBS than it did to CPP or dry eye disease.
Whether the findings will generalize to chronic pain conditions in men is unclear. The TwinsUK collection has more females than males because it was originally set up to look at conditions predominating in women. “I think it is too early to say whether the genetic variants for chronic pain will differ between the sexes,” Williams said.
Michele Solis is a science writer and former neuroscientist who lives in Seattle, Washington, US.
Image credit: ©iStockphoto.com/Alainjuteau
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