Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: analysis of a family-based cohort and twin study.

van Hecke, Oliver; Hocking, Lynne J.; Torrance, Nicola; Campbell, Archie; Padmanabhan, Sandosh; Porteous, David J.; McIntosh, Andrew M.; Burri, Andrea V.; Tanaka, Haruka; Williams, Frances M. K.; Smith, Blair H.

Abstract

Depression and chronic pain are the two most important causes of disability. They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender and deprivation) might explain the co-morbidity of these three conditions, we hypothesised that they co-occur, and may be due to shared familial risk and/or genetic factors. We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK. The study used standardised and validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status and deprivation. Secondly, using the same cohort, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions. Lastly, we examined similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI. Through this examination, we were able to independently replicate the findings. We were also able to explore the influence of various factors that might predispose an individual to co-occurring chronic widespread pain (CWP) and cardiovascular disease (i.e. hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). The specific factors considered were additive genetic factors (A), and shared (C) and non-shared (E) environmental factors. In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2.64 [95% CI 2.34–2.97]). Those with angina were four times more likely to have chronic pain (OR 4.19 [3.64–4.82]). Those with depression were twice as likely to have angina (OR 2.20 [1.90–2.54]). Similar odds were obtained when the outcomes and predictors were reversed, and similar effects were seen among sibling pairs: depression in one sibling predicted chronic pain in the other (OR 1.34 [1.05–1.71]), angina predicted chronic pain in the other (OR 2.19 [1.63–2.95]), and depression predicted angina in the other (OR 1.98 [1.49–2.65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression, compared with those manifesting neither trait (OR 3.78 [2.99–4.78]). Angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7.76 [6.05–9.95]), and chronic pain showed nine-fold increased odds in the presence of depression and angina (OR 9.43 [6.85–12.98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p < 0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2.2% [95% CI 0.06–0.23]). In conclusion, we found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort and a twins cohort), suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age, BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

Citation

VAN HECKE, O., HOCKING, L.J., TORRANCE, N., CAMPBELL, A., PADMANABHAN, S., PORTEOUS, D.J., MCINTOSH, A.M., BURRI, A.V., TANAKA, H., WILLIAMS, F.M.K. and SMITH, B.H. 2017. Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: analysis of a family-based cohort and twin study. PLoS ONE [online], 12(2), article ID e0170653. Available from: https://doi.org/10.1371/journal.pone.0170653

• Journal Article Type: Article
• Acceptance Date: Jan 9, 2017
• Online Publication Date: Feb 22, 2017
• Publication Date: Feb 22, 2017
• Deposit Date: Dec 11, 2019
• Publicly Available Date: Dec 12, 2019
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 2
• Article Number: e0170653
• DOI: https://doi.org/10.1371/journal.pone.0170653
• Keywords: Genetic predisposition; Chronic pain; Depression; Cardiovascular disease; Twins; Co-occurrence of chronic conditions
• Public URL: https://rgu-repository.worktribe.com/output/810522