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Clinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

Elvs ashagen T, Quintana DS, Reponen EJ, Mørch RH, Lunding SH, Vedal TSJ, Dieset I, Melle I, Lagerberg TV, Andreassen OA. Cardiovascular risk remains high in schizophrenia with modest improvements in bipolar disorder during past decade Objective: While CVD risk has decreased in the general population during the last decade, the situation in patients with schizophrenia (SCZ) and bipolar disorder (BD) is unknown. Methods: We compared CVD risk factors in patients with SCZ and BD recruited from 2002-2005 (2005 sample, N = 270) with patients recruited from 2006-2017 (2017 sample, N = 1011) from the same catchment area in Norway. The 2017 sample was also compared with healthy controls (N = 922) and the general population (N range = 1285-4587, Statistics Norway) from the same area and period. Results: Patients with SCZ and BD in the 2017 sample had significantly higher level of most CVD risk factors compared to healthy controls and the general population. There was no significant difference in the prevalence of CVD risk factors in SCZ between the 2005 and 2017 samples except a small increase in glucose in the 2017 sample. There were small-to-moderate reductions in hypertension, obesity, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure in the BD 2017 sample compared to the 2005 sample.Conclusion: Despite major advances in health promotion during the past decade, there has been no reduction in the level of CVD risk factors in patients with SCZ and modest improvement in BD. Significant outcomes• We found no improvement in CVD risk in patients with SCZ while patients with BD had small-tomoderate reductions in several risk factors during the past decade.• The striking increase in CVD risk factors in patients with SCZ and BD compared to the general population is a major clinical problem in psychiatry. Limitations• The study periods of the 2005 and 2017 samples are close, which may reduce the chance of detecting differences between the samples.• Fasting blood samples and information on daily smoking were retrieved from a subset of healthy controls, although a sufficiently large number for comparison with patients.