Neuropsychiatric Disorders and Constipation: Unraveling Causal Links Through Genetic Analysis

Numerous observational studies have suggested a relationship between neuropsychiatric disorders and constipation. However, the specific causal relationships remain unclear. Mendelian randomization (MR) serves as a proven strategy for examining the causal relationships between genetic exposures and outcomes. In the present study, we used a two-sample Mendelian randomization (TSMR) analysis to thoroughly explore the potential bidirectional genetic causal effects between neuropsychiatric disorders and constipation.

We utilized the R11 data from Finnish genome-wide association studies (GWAS) to examine the association between twelve common neuropsychiatric disorders and constipation using TSMR analysis. To establish this causal link, we applied the random-effects inverse variance weighting (IVW) method. Additionally, we conducted various sensitivity analyses, including MR-Egger analysis, weighted median analysis, and leave-one-out analysis, followed by heterogeneity testing. Finally, reverse MR testing was performed to further elucidate the potential causal relationship between constipation and neuropsychiatric disorders.

The forward MR results indicated that anxiety (IVW OR = 1.133; 95% CI: 1.021-1.258; p = 0.020) and depression (IVW OR = 1.149; 95% CI: 1.071-1.232; p = 0.000) may increase the risk of constipation. Reverse MR testing further confirmed that constipation increased the risk of anxiety (IVW OR = 1.273; 95% CI: 1.116-1.452; p = 0.000) and depression (IVW OR = 1.207; 95% CI: 1.095-1.331; p = 0.000) and was positively correlated with epilepsy (IVW OR = 1.331; 95% CI: 1.103-1.607; p = 0.003) and trigeminal neuralgia (IVW OR = 1.897; 95% CI: 1.225-2.936; p = 0.004). No pleiotropy or heterogeneity was observed in the MR analysis.

Our research elucidates the underlying bidirectional causal relationship between twelve common neuropsychiatric disorders and constipation. These findings emphasize the importance for clinical practitioners to prioritize the identification and management of constipation symptoms in patients with neuropsychiatric conditions, aiming to enhance their overall health and quality of life.