  Cardiovascular diseases (CVD) represent a major health issue in patients with
schizophrneia (SCZ) and bipolar disorder (BD), but the exact nature of
cardiometabolic (CM) abnormalities involved and the underlying mechanisms
remain unclear. Using polygenic risk scores (PRS) and LD score regression, we
investigated the shared genetic bases of SCZ and BD with a panel of 28
cardiometabolic traits. We performed Mendelian randomization (MR) to elucidate
casual relationships between the two groups of disorders. The analysis was
based on large-scale meta-analyses of genome-wide association studies (GWAS).
We also identified the potential shared genetic variants by a statistical
approach based on local true discovery rates, and inferred the pathways
involved. We found polygenic associations of SCZ with glucose metabolism
abnormalities, adverse adipokine profiles, increased wait-hip ratio and raised
visceral adiposity. However, BMI showed inverse genetic correlation and
polygenic link with SCZ. On the other hand, we observed polygenic associations
with an overall favorable CM profile in BD. MR analysis showed that SCZ may be
causally linked to raised triglyceride and that lower fasting glucose may be
linked to BD; otherwise MR did not reveal other significant causal
relationships in general. We also identified numerous SNPs and pathways shared
between SCZ/BD with cardiometabolic traits, some of which are related to
inflammation or the immune system. In conclusion, SCZ patients may be
genetically associated with several CM abnormalities independent of medication
side-effects, and proper surveillance and management of CV risk factors may be
required from the onset of the disease. On the other hand, CM abnormalities in
BD are more likely to be secondary.
