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Major depressive disorder and irritable bowel syndrome risk: A Mendelian randomization study
1Department of General Surgery, Traditional Chinese Medicine Hospital of Yangzhou, Yangzhou, China.
Background:
Previous studies have revealed a connection between major depressive disorder (MDD) and irritable bowel syndrome (IBS), but it remains obscure if the two diseases are related causally. Mendelian randomization was utilized in this investigation to ascertain whether MDD contributed to the emergence of IBS.
Methods:
To examine possible connections between MDD and IBS, we used two-sample Mendelian randomization (MR) utilizing summary data from genome-wide association studies (GWAS). The Psychiatric Genomics Consortium (PGC) provided information on genetic associations with MDD (cases: 135,458; controls: 344,901). The Medical Research Council Integrative Epidemiology Unit (MRC-IEU) provided information on genetic associations with IBS (cases:10,939; controls:451,994). Inverse Variance Weighted (main analyses), MR-Egger regression, Weighted mode, and Weighted Median were the four MR methods used in this investigation. In addition, we also performed multiplicity and heterogeneity analyses to eliminate possible biases.
Results:
In the standard Inverse Variance Weighting (IVW) method, an increased risk of IBS was linked to a genetic susceptibility to MDD (OR: 1.01; 95% CI: 1.006 to 1.014, p = 1.02E-07). In addition, neither significant heterogeneity (IVW Q = 24.80, p = 0.73) nor horizontal pleiotropy (MR Egger p = 0.17; MRPRESSO p = 0.54) were detected in this MR analysis. The bidirectional analysis, however, did not show a genetic link between IBD and MDD (p steiger <0.01).
Conclusion:
A direct causal relationship between MDD and IBS was revealed by Mendelian randomization study, which contributes to the effective clinical management of both diseases.
Insights
Major depressive disorder (MDD) significantly increases the risk of developing irritable bowel syndrome (IBS). This Mendelian randomization study confirms a causal link, aiding in the clinical management of both conditions.
Area of Science:
- Genetics
- Gastroenterology
- Psychiatry
Background:
- Previous research suggests a link between major depressive disorder (MDD) and irritable bowel syndrome (IBS).
- The causal relationship between MDD and IBS remains unclear.
- This study investigates if MDD causally contributes to IBS development.
Purpose of the Study:
- To determine if genetic susceptibility to MDD increases the risk of IBS.
- To explore the causal relationship between MDD and IBS using Mendelian randomization.
Main Methods:
- Two-sample Mendelian randomization (MR) using summary data from large genome-wide association studies (GWAS).
- Data for MDD from the Psychiatric Genomics Consortium (N=480,367).
- Data for IBS from the Medical Research Council Integrative Epidemiology Unit (N=462,933).
- Analyzed using Inverse Variance Weighted (IVW), MR-Egger, Weighted Mode, and Weighted Median methods.
- Performed heterogeneity and pleiotropy analyses to ensure robustness.
Main Results:
- A significant causal effect of MDD on IBS risk was observed (OR: 1.01; 95% CI: 1.006-1.014; P=1.02E-07) using the IVW method.
- No significant heterogeneity or horizontal pleiotropy was detected, supporting the validity of the findings.
- Bidirectional analysis did not reveal a genetic link between IBS and MDD.
Conclusions:
- Mendelian randomization provides evidence for a direct causal relationship between MDD and IBS.
- These findings can inform clinical strategies for managing patients with both MDD and IBS.
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