Associations of Schizophrenia and Major Depressive Disorder with Constipation: A Mendelian Randomization Study.

Objective: Psychiatric disorders have been associated with Constipation in observational studies, although their causal relationships remain uncertain. We used Mendelian randomization analysis to infer causality between Schizophrenia and Major Depressive Disorder with Constipation.

Methods: The exposure of interest was Psychiatric disorders, including Schizophrenia (SCZ) and Major Depressive Disorder (MDD). Summary statistics for psychiatric disorders were recruited from the PGC, SCZ (30,490 cases and 312,009 controls), MDD (170,756 cases and 329,443 controls), whereas Constipation summary genetic data were obtained from a FinnGen involving 17,246 cases and 201,546 controls. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between SCZ and MDD with Constipation.

Results: LDSC indicated that Constipation was genetically correlated with Psychiatric disorders (r _g range: |0.04-0.05). The Mendelian randomization analysis indicated that there was significant evidence that genetically determined SCZ (OR = 1.05, 95% CI = 1.02-1.07, P<0.01) and MDD (OR = 1.21, 95% CI = 1.10-1.33, P<0.01) were statistically significantly causally associated with the risk of Constipation. SCZ effects remained within the range of practical equivalence (ROPE).

Conclusion: The Mendelian randomization analysis suggested that SCZ and MDD increase the risk of Constipation. However, the association between SCZ and constipation, predominantly within the ROPE range, suggested only limited clinical implications.