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Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders. Mental disorders are often linked with cardiometabolic disorders, but the mechanism remains unclear. Here, the authors use comprehensive health data from Denmark and to shed light on the genetic and environmental factors influencing the co-occurrence of six mental disorders and 15 cardiometabolic disorders. [ABSTRACT FROM AUTHOR]

Eating disorders (ED) are mental disorders associated with high levels of morbidity, mortality, and social, psychological and physical impairment. Currently, eating disorders are more prevalent in women, yet they affect people from all sectors of society (i.e., sex, ancestry, sexual orientation, age etc). Lifetime prevalence estimates of ED vary dramatically between studies. This high level of variability is likely due to sample size variations, differences in diagnostic practices, and ascertainment biases (e.g., clinical vs population wide sampling). These biases influence downstream estimates of the genetic contribution to the liability of EDs. Consequently, while family, twin, and adoption studies have shown that genetic factors contribute to the risk of developing an eating disorder, the variability in estimates is substantial. This highlights the need for large population representative studies. Here, we estimated the heritability of three eating disorders (anorexia, bulimia, and ED NOS) and the genetic correlations between them and seven other mental disorders using information from nationally collected civil- and medical registers in Denmark (>6 million) and Sweden (>13 million). These registers contain information about all individuals in the two Nordic countries during roughly the last 100 years, their extended genealogy, and all hospital records. Both datasets reflect a total population, uniformly diagnosed across the country in a nationally run public healthcare system. Therefore, the effect of different kinds of biases associated with cohorts ascertained from (psychiatric) clinics or voluntary participants is reduced. Using Danish data, we showed that all eating disorders were heritable (h2: 0.28–0.35) and presented substantial positive genetic correlations with other mental disorders (rG: 0.23–0.63 (anorexia); 0.24–0.46 (bulimia); 0.42–0.73 (ED NOS)). While there is some variation, all genetic correlations presented overlapping confidence intervals. OCD showed the largest genetic correlation with both Anorexia and ED NOS. A similar association was observed using genotype-based estimates of genetic correlations. Eating disorders, especially anorexia, are commonly observed comorbid with OCD and anxiety phenotypes. The observed large genetic correlations with eating disorders point to a substantial relevance of shared genetic effects as a partial explanation for those clinical observations. The same pattern of results was observed using the larger Swedish data, indicating a high degree of similarity between countries. From the sex-stratified analyses, we observed that the female estimates were nearly identical to the main results, while the male estimates could not be considered reliable. These results suggest that due to the substantial difference in ED prevalence between males and females, and despite using the complete data of two Nordic countries, the estimations we observed by using males and females together are driven by the female samples and that we are underpowered to estimate heritability and genetic correlations in males. Here, using unascertained population-wide register data of two Nordic countries representing 20 million people, we have shown that eating disorders are complex heritable outcomes with substantial evidence for partially shared genetic risk across many mental disorders. [ABSTRACT FROM AUTHOR]

Importance: There is emerging evidence that spouses of patients with cancer may have a higher prevalence of mental illness, but these studies have been limited by pre-post designs, focus on a single mental illness, and short follow-up periods., Objectives: To assess the overall burden of psychiatric disorders among spouses of patients with cancer vs spouses of individuals without cancer and to describe possible changes in this burden over time., Design, Setting, and Participants: This population based cohort study included spouses of patients with cancer (diagnosed 1986-2016 in Denmark and 1973-2014 in Sweden; exposed group) and spouses of individuals without cancer (unexposed group). Members of the unexposed group were individually matched to individuals in the exposed group on the year of birth, sex, and country. Spouses with and without preexisting psychiatric morbidity were analyzed separately. Data analysis was performed between May 2021 and January 2022., Exposures: Being spouse to a patient with cancer., Main Outcomes and Measures: The main outcome was a clinical diagnosis of psychiatric disorders through hospital-based inpatient or outpatient care. Flexible parametric models and Cox models were fitted to estimate hazard ratios (HRs) with 95% CIs, adjusted for sex, age and year at cohort entry, country, household income, and cancer history., Results: Among 546 321 spouses in the exposed group and 2 731 574 in the unexposed group who had no preexisting psychiatry morbidity, 46.0% were male participants, with a median (IQR) age at cohort entry of 60 (51-68) years. During follow-up (median, 8.4 vs 7.6 years), the incidence rate of first-onset psychiatric disorders was 6.8 and 5.9 per 1000 person-years for the exposed and unexposed groups, respectively (37 830 spouses of patients with cancer [6.9%]; 153 607 of spouses of individuals without cancer [5.6%]). Risk of first-onset psychiatric disorders increased by 30% (adjusted HR, 1.30; 95% CI, 1.25-1.34) during the first year after cancer diagnosis, especially for depression (adjusted HR, 1.38; 95% CI, 1.30-1.47) and stress-related disorders (adjusted HR, 2.04; 95% CI, 1.88-2.22). Risk of first-onset psychiatric disorders increased by 14% (adjusted HR, 1.14; 95% CI, 1.13-1.16) during the entire follow-up, which was similar for substance abuse, depression, and stress-related disorders. The risk increase was more prominent among spouses of patients diagnosed with a cancer with poor prognosis (eg, pancreatic cancer: adjusted HR, 1.41; 95% CI, 1.32-1.51) or at an advanced stage (adjusted HR, 1.31; 95% CI, 1.26-1.36) and when the patient died during follow-up (adjusted HR, 1.29; 95% CI, 1.27-1.31). Among spouses with preexisting psychiatric morbidity, the risk of psychiatric disorders (first-onset or recurrent) increased by 23% during the entire follow-up (adjusted HR, 1.23; 95% CI, 1.20-1.25)., Conclusions and Relevance: In this cohort study of 2 populations in Denmark and Sweden, spouses of patients with cancer experienced increased risk of several psychiatric disorders that required hospital-based specialist care. Our results support the need for clinical awareness to prevent potential mental illness among the spouses of patients with cancer.