Genetically determined risk of mood swings and cardiometabolic diseases: mendelian randomization study

Abstract

Abstract Background Mood swings is believed to associated with increased risk of Cardiometabolic Diseases (CMD). However, the roles of mood swings on CMD are controversial because of the bias of reverse causation and/or confounding in epidemiological studies. Hence, we use a two-sample MR approach to identify the causal association between genetically determined mood swings and CMD. Methods We obtained 33 independent single-nucleotide polymorphisms (SNPs) with genome-wide significant (P<5×10–8) associated with mood swings as instrumental variable in UK Biobank. Summary data of outcomes were extracted from the Coronary Artery Disease Genome-wide Replication and Meta-analysis plus the Coronary Artery Disease Genetics consortium, the Diabetes Genetics Replication and Meta-analysis consortium, the CKDGen consortium, and the International Stroke Genetics Consortium. Results The genetic instrument of 33 SNPs explained 4.8% of the variance in mood swings. Genetically determined mood swings was associated with an increased risk of coronary artery disease (CAD) (odds ratio 3.12, 95% confidence interval 1.92 to 5.08; P=4.32×10–6). However, mood swings had no effect on the other cardiometabolic outcomes. The above estimates were consistent across all three MR methods without significant heterogeneity. Also, there was no evidence of directional pleiotropy for each outcome except for large artery stroke. Conclusions Using MR approaches that are able draw causal inference, our results suggest that interventions aimed at improving mood swings in the population would lead to a reduction risk of CAD, which highlights the importance of mood management in high-risk CAD population. Funding Acknowledgement Type of funding sources: None.