Shared genetic factors underlie chronic pain syndromes

Abstract

Chronic pain syndromes (CPS) are highly prevalent in the general population, and increasingly the evidence points to a common etiological pathway. Using a large cohort of twins (n=8564) characterized for chronic widespread musculoskeletal pain (CWP), chronic pelvic pain (PP), migraine (MIG), dry eye disease, and irritable bowel syndrome (IBS), we explored the underlying genetic and environmental factors contributing to CPS and the correlation between them. The sample was predominantly female (87.3%), with a mean age of 54.7 (±14.7) years. Prevalence of the different CPS ranged from 7.4% (PP) to 15.7% (MIG). For all CPS the within-twin correlation in monozygotic twin pairs was higher than in dizygotic pairs, suggesting a heritable component. Estimated heritability ranged from 19% (IBS) to 46% (PP). Except for MIG, we found significant pairwise phenotypic correlations between the CPS. The phenotypic correlation was highest between CWP and IBS (0.40; 95% confidence interval: 0.27 to 0.46). Excluding MIG from further analyses, cross-twin cross-trait correlations were higher in monozygotic compared with dizygotic twin pairs, suggestive of shared genetic factors between CWP, PP, IBS, and dry eye disease. Twin modeling analysis revealed the common pathway model as the model best explaining the observed pattern of correlation between the traits, with an estimated heritability of 66% of the underlying latent variable. These results are evidence of shared genetic factors in conditions manifesting chronic pain and justify the search for underlying genetic variants.

Sex differences in clinical characteristics of dry eye disease

“…21 In an extended sample of this twin cohort we have shown that the chronic pain syndromes irritable bowel syndrome, fibromyalgia and pelvic pain show shared genetic factors with DED, indicating that DED is, at least partly, part of a spectrum of chronic pain disorders. 22 So, given all these findings together, it might not be surprising that the present study found women to have lower correlation between symptoms and signs. That dry eye involves more than the ocular surface alone is increasingly recognized.…”

Patients with more severe symptoms of neuropathic ocular pain report more frequent and severe chronic overlapping pain conditions and psychiatric disease

“…35 This suggests that shared mechanisms underlying somatosensory dysfunction may account for the coexistence of comorbid conditions despite very different demographics in our independent cohorts. 33 Consistent with the biopsychosocial model of chronic pain, it is not surprising that those with more severe NOP complaints also had less healthy mental health indices. The frequent observation of COPC in some patients has suggested that there may be shared genetic bases for these disorders.…”

Prevalence and risk factors of dry eye disease in a British female cohort

“…The findings of this study suggest that DED might be added to this spectrum of disorders. Indeed, we recently explored this relationship in a multivariate twin study, showing evidence that a common pathway with shared genetic factors underlies DED and the chronic pain syndromes pelvic pain, IBS, CWPS 19. Interestingly, Türkyilmaz et al 20 have shown an increased tear osmolarity and lowered tear break-up time and Schirmer's test value in patients with CWPS without any concomitant (rheumatological) disease, suggesting a possible pathophysiological link next to chronic pain disposition.…”