Background: This study aimed to investigate putative causal effects between constipation and stroke using bidirectional Mendelian randomization (MR) analysis.
Methods: Based on the cross-sectional study, logistic regression models were developed to assess the association between constipation and stroke prevalence. Subsequently, genome-wide association studies statistics were employed to perform MR analysis between constipation and stroke, as well as its subtypes. The inverse variance weighting (IVW) method was the primary method, complemented by four additional methods, namely weighted median, weighted mode, simple mode, and MR-Egger regression. Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier, and MR Steiger test were performed to assess heterogeneity and pleiotropy effects.
Results: Constipation was associated with a greater risk of stroke even after adjusting for all covariates in logistic regression [odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.01-2.09, p = 0.042]. IVW MR analysis revealed that constipation affected large artery atherosclerosis (LAS; IVW OR = 1.5, 95% CI = 1.07-2.104, p = 0.019). No significant or suggestive association was observed with the risk of stroke or its various subtypes in MR analysis. Meanwhile, reverse MR analysis revealed no significant causal relationship between stroke or other stroke subtypes and constipation. The results of sensitivity analyses revealed no significant horizontal pleiotropy affecting causal estimates.
Conclusion: While cross-sectional studies have established that constipation increases the risk of stroke, this two-sample bidirectional MR analysis revealed a positive correlation between constipation and LAS. However, no such correlation was observed between constipation and stroke, including its various subtypes.
Keywords: Mendelian randomization analysis; constipation; ischemic stroke; large-artery atherosclerotic stroke; stroke.
Copyright © 2023 Du, Yang, Zhou, Wu, Cai, Meng, Teng and He.