Objective To systematically explore the potential causal relationship between dementia and constipation using a two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary data of dementia (exposure factor) and constipation (outcome variable) were extracted from the FinnGen database, and single nucleotide polymorphisms (SNPs) strongly associated with the exposure factor were strictly screened out as instrumental variables. The inverse-variance weighted (IVW) method was employed as the primary analytical approach to estimate causal effects, complemented by weighted median estimation (WME) method, MR-Egger regression method, and weighted mode (WM) method. The MR-Egger regression intercept and MR-PRESSO global test were used to evaluate horizontal pleiotropy; Cochran's Q test was applied to assess heterogeneity among instrumental variables; leave-one-out sensitivity analysis was performed to evaluate the influence of an individual SNP on the overall causal effect; Steiger directionality test was used to verify the causal relationship direction. Results A total of 16 qualified SNPs were finally included in this study as instrumental variables. The IVW method results indicated a statistically significant positive causal relationship between dementia and constipation (OR=1.037, 95%CI: 1.008-1.067, P=0.012). The results obtained using the WME and WM methods were consistent with those of the IVW method in direction and both were statistically significant (all P<0.05). Although the causal effect estimation from the MR-Egger regression method did not reach statistical significance, its direction was consistent with the IVW method (OR=1.026, 95%CI: 0.983-1.071, P=0.259). Neither MR-Egger regression intercept nor MR-PRESSO global test suggested statistically significant horizontal pleiotropy (all P>0.05); Cochran's Q test showed no statistically significant heterogeneity among instrumental variables (P>0.05). Leave-one-out sensitivity analysis demonstrated that removing an single SNP did not substantially alter the overall causal effect, indicating the causal effect estimation was not driven by an individual SNP. The Steiger directionality test supported the causal hypothesis direction of “dementia → constipation”. Conclusion Genetic evidence from MR analysis supports a positive causal association between dementia and constipation, suggesting that dementia may be a risk factor for constipation.

无