Phenotypic Associations and Shared Genetic Etiology between Bipolar Disorder and Cardiometabolic Traits

Background People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. BPD has a bidirectional relationship with cardiometabolic traits, but their shared etiology is poorly understood. This study aimed to examine the phenotypic associations and shared genetic etiology between BPD and various cardiometabolic traits. Methods In a subset of the UK Biobank sample ( N = 67,317) we investigated phenotypic associations between BPD ( n = 4,155) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine the shared genetic etiology, polygenic risk scores and genetic correlations were calculated between BPD and these traits. Results Several cardiometabolic traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin (HbA 1c ), low systolic blood pressure, high body mass index, high waist-to-hip ratio, as well as stroke, coronary artery disease and type 2 diabetes diagnosis. Polygenic risk score regressions showed that higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease, and type 2 diabetes was associated with increased risk for bipolar disorder. These associations were not replicated when using genetic correlations. Conclusions This large study identified phenotypic cardiometabolic risk factors for BPD. Moreover, it found that comorbidities between BPD and waist-to-hip ratio, triglycerides, type 2 diabetes and coronary artery disease may be based on shared genetic etiology. These results provide a better understanding of the phenotypic and genetic comorbidity between BPD and cardiometabolic traits.