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. 2024 Dec 19;23(1):50.
doi: 10.1186/s12991-024-00537-7.

Mood instability and risk of gastrointestinal diseases - a univariable and multivariable mendelian randomization study

Rui-Lin Liu #  1 , Qing-Chun Song #  1 , Li-Ming Liu  1 , Yi-Feng Yang  2 , Wei-Hong Zhu  3   4
Affiliations

Mood instability and risk of gastrointestinal diseases - a univariable and multivariable mendelian randomization study

Rui-Lin Liu et al. Ann Gen Psychiatry. .

Abstract

Background: Mood instability, characterized by sudden and unpredictable mood shifts, is prevalent in psychiatric disorders and as a personality trait. Its association with gastrointestinal diseases has been recognized but remains poorly understood in terms of causality.

Methods: This study aims to investigate the causal relationship between mood instability and a spectrum of gastrointestinal diseases by univariable and multivariable mendelian randomization analysis. The exposure and outcome data were retrieved from the IEU open GWAS database, the UK biobank and the FinnGen study. Instrumental variables were selected to meet relevance, independence, and exclusion restriction criteria. GWAS datasets for mood instability and 28 gastrointestinal diseases were utilized, incorporating diverse populations and genders. Univariable and multivariable Mendelian randomization analyses were conducted using R software. MR statistics from different datasets for the same disease were meta-analyzed to maximize the study population.

Results: In univariable MR analysis, genetic predisposition to mood instability showed significant associations with increased risk for several gastrointestinal diseases, including: gastroesophageal reflux disease, gastric ulcer, acute gastritis, irritable bowel syndrome, internal hemorrhoids, cirrhosis, cholecystitis, cholelithiasis, acute pancreatitis, chronic pancreatitis. In multivariable MR analysis, after adjusting for major depression, bipolar disorder, anxiety disorder, and schizophrenia, associations with the following gastrointestinal diseases remained statistically significant: internal hemorrhoids, cirrhosis, acute pancreatitis, chronic pancreatitis.

Conclusion: This study provides compelling evidence for a potential causal relationship between mood instability and certain gastrointestinal diseases underscoring the importance of considering mood instability as a potential risk factor for gastrointestinal diseases as well as the positive role of maintaining mood stability in the prevention of gastrointestinal disorders.

Keywords: Gastrointestinal disease; Mendelian randomization; Mood instability.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: We used summary-level data from publicly available GWAS studies which have received ethical approval from their respective institutional review boards and informed consent from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of the present study design. MR, Mendelian randomization; MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier; SNP, single nucleotide polymorphism
Fig. 2
Fig. 2
Summary of associations of genetically predicted mood swings and experiencing mood swings with 28 gastrointestinal diseases after meta. UVMR, univariable Mendelian randomization; MVMR, multivariable Mendelian randomization. The number in the box are odds ratios for associations of mood instability to 28 gastrointestinal diseases, and the green means p values are less than 0.05 and statistically significant
Fig. 3
Fig. 3
Forest plot of genetically predicted mood instability with 10 gastrointestinal diseases in univariable Mendelian randomization analysis. The green bar means the diseases were associated with genetic susceptibility to mood swing, and yellow bar means the diseases were associated with genetic susceptibility to experiencing mood swings
Fig. 4
Fig. 4
Forest plot of genetically predicted mood instability with 4 gastrointestinal diseases in multivariable Mendelian randomization analysis. The green bar means the diseases were associated with genetic susceptibility to mood swing, and yellow bar means the diseases were associated with genetic susceptibility to experiencing mood swings
See this image and copyright information in PMC

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