Table 1.

Summary of Key Epidemiological Studies of Comorbidity

Study (Year)	Design	Sample Size	Key Finding	Limitation	Evidence Level	Key References
Zheng et al 2025	Bidirectional MR (UK Biobank, FinnGen)	~500,000	MD causally associated with constipation (OR = 1.28)	No reverse causality found; constipation-specific instruments limited	MR	[10]
Huang et al 2025	Cross-sectional + MR	12,000	38–52% comorbidity prevalence	Cross-sectional design	Cross-sectional / MR	[2]
Yun et al 2024	Population cohort	35,000	Constipation precedes depression by 1–5 years	Observational; residual confounding	Cohort	[5]
Refractory Constipation Study 2025	Retrospective cohort	610	Anxiety, depression, and somatic symptoms independent risk factors for refractoriness (AUC = 0.81)	Retrospective design; single center	Cohort	[13]