Association between psychiatric disorders and irritable bowel syndrome: A bidirectional Mendelian randomization study.

ABSTRACT

OBJECTIVE: Previous studies have suggested that irritable bowel syndrome (IBS) is strongly associated with psychiatric disorders. However, it is unclear whether this association is causal, concomitant, or accidental. Thus, we performed Mendelian randomization (MR) analysis to evaluate the causal effects of several psychiatric disorders on IBS. METHODS: Summary data of genome-wide association studies (GWASs) were obtained mainly from the Psychiatric Genomics Consortium (PGC) on individuals of European ancestry and from a recent GWAS on IBS. We used three MR methods, the inverse-variance weighting (IVW), weighted median (WM), and MR-Egger regression (MR-Egger). In addition, two other indicators, namely, the MR-IVW Cochran's Q statistic and MR-Egger intercept, were used to assess heterogeneity and detect directional horizontal pleiotropy, respectively. RESULTS: Heritability was high for bipolar disorder (81.18 %, 95 % CI = 73.18-148.18 %), schizophrenia (33.88 %, 95 % CI = 33.57-38.19 %), and panic disorder (30.66 %, 95 % CI = 20.74-40.58 %). For other disorders, there was a low liability-scale SNP heritability for major depressive disorder (MDD) (0.67 %, 95 % CI = 0.61-0.73 %), anxiety disorder (7.63 %, 95 % CI = 1.67-13.59 %), PTSD (0.96 %, 95 % CI = 0.12-1.8 %), and IBS (2.44 %, 95 % CI = 2.13-2.75 %). We also observed that schizophrenia had a significant causal effect on IBS according to MR-IVW. Notably, the individual causal estimates of genetic instruments for MDD and schizophrenia were heterogeneous, but no pleiotropic effects were observed. CONCLUSIONS: Our analyses revealed the causal effects of MDD and schizophrenia on IBS, a matter that has been subject to debate for decades, and also showed that IBS had causal effects on MDD.