Relationships between emotional states, bipolar disorder, and gastrointestinal disorders: A two-sample Mendelian randomization study

Abstract

BackgroundFunctional gastrointestinal symptoms are frequently observed in patients with bipolar affective disorder, but the causal relationship between these conditions remains unclear. To establish causality, this study utilized Mendelian randomization (MR) with data from large-scale genomic research. The investigation aimed to elucidate the relationship between emotional states, bipolar disorder, and functional gastrointestinal disorders (FGIDs). MethodsSummary statistics from GWAS were utilized for mood swings (UK biobank, N = 451,619), irritable mood (UK biobank, N = 373,733), bipolar disorder (UK biobank, N = 352,006),functional dyspepsia (FinnGen biobank, N = 194,071), and irritable bowel syndrome (UK biobank, N = 486,601). All GWAS summary statistics were derived from individuals of European ancestry. The primary analysis employed the inverse variance-weighted method for Mendelian randomization (MR). Additionally, we conducted tests for heterogeneity and pleiotropy to ensure the robustness of our results. ResultsA suggestive positive causal relationship was identified between mood swings-related conditions and IBS using the inverse variance-weighted (IVW) method [mood swings-IBS: OR/95%CI: 3.221(2.417,4.294), P(1.42E−15); irritable mood-IBS: OR/95%CI: 1.881(1.615,2.191), P(4.56E−16); bipolar disorder-IBS: OR/95%CI: 1.003(1.001,1.006), P(0.009)]. For functional dyspepsia, a suggestive positive causal relationship was observed with mood swings [mood swings-FD: OR/95%CI: 2.827(1.124,7.109), P(0.027)]. In the reverse analysis, causal relationship was observed between IBS and emotional states [IBS and mood swings: OR/95%CI: 1.030(1.021,1.040), P(1.10E−10); IBS and irritable mood: OR/95%CI: 1.064(1.041,1.087), P(2.58E−08)]. ConclusionsMood swings, irritable mood, and bipolar disorder were associated with an increased risk of functional gastrointestinal disorders (FGIDs). Additionally, reverse analysis revealed a causal relationship between irritable bowel syndrome (IBS) and both mood swings and irritable mood. These findings suggest that targeted emotional interventions may be beneficial for patients with FGIDs. Further research is warranted to explore the relationship between mood instability-related disorders and FGIDs, particularly IBS.