Bidirectional genetic overlap between mood swings and irritable bowel syndrome

Mood swings and irritable bowel syndrome (IBS) are closely related. However, the reason for the clinical concurrence of this phenomenon is unknown, and maybe it is because the two share genetic underpinnings.

Genome-wide association studies (GWAS) of mood swings and IBS data were used for the study. Genetic correlation was assessed using the linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA method. Two-sample Mendelian randomization (TwoSampleMR) was used to explore the causal relationship between the two conditions. The conditional/conjoint false discovery rate (cond/conjFDR) was used for genetic overlap analysis. Finally, LDSC applied to specific expression gene analysis was performed to identify tissues associated with the two conditions.

At the genomic level, mood swings and IBS have global and local genetic correlations. Analysis of the two traits by Mendelian randomization revealed a bidirectional causal relationship. We identified 21 genetic risk loci (concFDR < 0.05) shared by mood swings and IBS, which acted in the same direction on the two traits. Additionally, mood swings and IBS shared 11 sites in the brain tissues as origins.

The present study suggests the existence of polygenic overlap between mood swings and IBS and provides novel insights into the genetic underpinnings and mechanisms of comorbidities occurring in these two conditions.