Schizophrenia and major depressive disorder (MDD) may be genetically associated with increased risk for constipation but only the latter association appears to be clinically significant, according to results of a Mendelian randomization study published in Clinical and Experimental Gastroenterology.

Constipation, a common and often debilitating gastrointestinal disorder affecting an estimated 10.4% of the global population, is more prevalent among older adults and individuals with mental health conditions. Although previous studies have linked psychiatric disorders to constipation, the causal mechanisms underlying these associations remain unclear.

To explore this relationship, researchers utilized genome-wide association study data extracted from Psychiatric Genomics Consortium 2021 and 2022 datasets. The study included psychiatric data captured from individuals of European ancestry with schizophrenia (n=30,490) or MDD (n=170,756), as well as control groups of individuals without these conditions (n=312,009 and n=329,443, respectively). FinnGen summary statistics were used to extract data from 17,246 individuals with constipation and 201,546 without constipation (controls). Genetic correlations were evaluated using linkage disequilibrium score regression and genome-wide association study summary statistics for schizophrenia and MDD. Causal effects were estimated via inverse-variance weighting, with schizophrenia and MDD assessed as exposures of interest and constipation as the primary outcome.

Our study provides suggestive evidence that genetically increasing odds of SCZ and MDD are statistically significantly associated with the risk of Constipation.

Significant genetic correlations were found between constipation and both psychiatric disorders. For schizophrenia, the genetic correlation coefficient was 0.0423 (P <.05), while for MDD, it was 0.0517 (P <.05). Mendelian randomization analysis demonstrated a causal association between schizophrenia and constipation (odds ratio [OR], 1.05; 95% CI, 1.02-1.07; P <.01). This relationship was supported by complementary analyses, including MR-Egger and weighted median methods. Instrument strength was robust (mean F-statistic, 291), with no evidence of heterogeneity (Cochran Q, P =.11) or horizontal pleiotropy (Egger intercept, P =.81).

The researchers also observed a causal relationship between MDD and constipation (OR, 1.21; 95% CI, 1.10-1.33; P <.01). Weighted median analysis further supported this finding (OR, 1.19; 95% CI, 1.03-1.38, P =.02). Heterogeneity and horizontal pleiotropy testing confirmed the validity of these results (Cochran Q, P =.09 and Egger intercept, P =.39), and instrument strength remained strong (mean F-statistic, 291).

In patients with constipation, the researchers noted significantly higher risks for somatization, psychosis, and symptoms of depression and anxiety.

Limitations of the study include its focus on individuals of European ancestry, which may limit generalizability; exclusion of other psychiatric disorders and subtypes of constipation; and lack of bidirectional analysis of Mendelian randomization causality between constipation and psychotic disorders.

According to the researchers, “Our study provides suggestive evidence that genetically increasing odds of SCZ [schizophrenia] and MDD are statistically significantly associated with the risk of Constipation.”

This article originally appeared on Gastroenterology Advisor

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