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

BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). 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, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, 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, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). 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 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, angina (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 nine-fold 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]). CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, 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

Multimorbidity among registered immigrants in Norway: the role of reason for migration and length of stay

Objectives International migration is rapidly increasing worldwide. However, the health status of migrants differs across groups. Information regarding health at arrival and subsequent periodic follow-up in the host country is necessary to develop equitable health care to immigrants. The objective of this study was to determine the impact of the length of stay in Norway and other sociodemographic variables on the prevalence of multimorbidity across immigrant groups (refugees, labour immigrants, family reunification immigrants and education immigrants). Methods This is a register-based study merging data from the National Population Register and the Norwegian Health Economics Administration database. Sociodemographic variables and multimorbidity across the immigrant groups were compared using Persons’ chi-square test and anova as appropriate. Several binary logistic regression models were conducted. Results Multimorbidity was significantly lower among labour immigrants (OR (95% CI) 0.23 (0.21–0.26) and 0.45 (0.40–0.50) for men and women, respectively) and education immigrants (OR (95% CI) 0.40 (0.32–0.50) and 0.38 (0.33–0.43)) and higher among refugees (OR (95% CI) 1.67 (1.57–1.78) and 1.83 (1.75–1.92)), compared to family reunification immigrants. For all groups, multimorbidity doubled after a five-year stay in Norway. Effect modifications between multimorbidity and sociodemographic characteristics across the different reasons for migration were observed. Conclusions Multimorbidity was highest among refugees at arrival but increased rapidly among labour immigrants, especially females. Health providers need to ensure tailor-made preventive and management strategies that take into account pre-migration and post-migration experiences for immigrants in order to address their needs