The association between constipation and stroke based on the NHANES and Mendelian randomization study

Area of Science:

• Cardiovascular Epidemiology
• Gastroenterology
• Neurology

Background:

• Cross-sectional studies suggest a link between constipation and increased stroke risk.
• Understanding the causal relationship between constipation and stroke is crucial for public health.
• Investigating potential genetic predispositions may elucidate underlying mechanisms.

Purpose of the Study:

• To investigate the putative causal effects between constipation and stroke using bidirectional Mendelian randomization (MR) analysis.
• To assess the association between constipation and stroke prevalence using logistic regression.
• To examine the causal relationship between constipation and stroke subtypes.

Main Methods:

• Bidirectional Mendelian randomization (MR) analysis utilizing genome-wide association studies statistics.
• Logistic regression models to assess cross-sectional associations.
• Primary analysis using the inverse variance weighting (IVW) method, supported by sensitivity analyses (weighted median, weighted mode, simple mode, MR-Egger regression).
• Tests for heterogeneity and pleiotropy (Cochran's Q, MR-Egger intercept, MR-PRESSO, MR-Steiger).

Main Results:

• Logistic regression indicated constipation is associated with a greater risk of stroke (OR=1.46, p=0.042).
• MR analysis revealed a significant association between constipation and large artery atherosclerosis (LAS) (IVW OR=1.5, p=0.019).
• No significant causal association was found between constipation and overall stroke risk or its subtypes in MR analysis. Reverse MR analysis also showed no significant causal relationship.

Conclusions:

• While cross-sectional data suggest constipation increases stroke risk, this MR study found a positive correlation specifically with large artery atherosclerosis (LAS).
• The study did not establish a causal link between constipation and overall stroke or its subtypes via MR analysis.
• Sensitivity analyses indicated no significant horizontal pleiotropy affecting the causal estimates.