Familial coaggregation and shared genetic loading of mental disorders and cardiovascular diseases

BACKGROUND: The high comorbidity between mental and cardiovascular diseases is widely recognized, but the underlying mechanisms are not yet well understood. We investigated the familial coaggregation and shared genetic loading between these diseases. METHODS: Using claims data from Taiwan's universal health insurance program, we identified cohorts of 4,513,509 individuals with parental information and 3,330,181 with full-sibling information born between 1970 and 1999, and followed up until 2020. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. Multiple logistic regression models were used to estimate the association of parental history, full-sibling history, and polygenic risk scores (PRSs) for severe mental illnesses (schizophrenia, bipolar disorder, major depressive disorder [MDD]) with the risk of myocardial infarction, stroke, peripheral arterial disease (PAD), and heart failure. RESULTS: Individuals with a parental history of schizophrenia, bipolar disorder, or MDD were more likely to have stroke and PAD. Coaggregation in full-siblings was observed for MDD with myocardial infarction and heart failure, bipolar disorders with stroke, and schizophrenia with PAD. The PAD risk increased with more relatives affected by MDD; the magnitude of association was larger when both parents were affected than when either parent was affected, and when there were two affected siblings than in those with only one. MDD PRS was positively associated with the risk of myocardial infarction and PAD. CONCLUSIONS: This study revealed familial coaggregation between mental and cardiovascular diseases, and shared polygenic liability of MDD with cardiovascular diseases. Our findings suggest the potential benefit of family-based integrated screening and preventive strategies.