Causal association between interleukin and constipation: A Mendelian randomization analysis / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To explore the causal association between interleukin (IL) level and constipation by using two-sample Mendelian randomization. 【Methods】 Analyses were performed based on the data from gene-wide association studies (GWAS). Both interleukin and constipation data were obtained from European populations. IL as an exposure variable was obtained from two GWAS data sets ⅰ. from a genetic map of the human plasma proteome containing 3 301 samples; ⅱ. from a GWAS data set on 90 circulating proteins, containing 30 931 samples. Constipation as an outcome variable was obtained from two GWAS data sets ⅰ. from Finngene, containing 26919 cases and 282235 controls; ⅱ. from UKBiobank, containing a total of 3 328 cases and 459682 controls. Single nucleotide polymorphisms strongly associated with exposure variables were used as instrumental variables, with inverse variance weighted (IVW) as the main analysis method, MR-egger regression and weighted median method as supplementary evidence for IVW results, and horizontal pleiotropy and heterogeneity were tested to ensure the stability of the results. 【Results】 In both of the two different outcome variables GWAS data, IVW analysis results showed that decreased level of IL-17 receptor C was associated with an increased risk of constipation, with ORs of 0.956 (95% CI 0.916-0.997, P=0.036‖Finngene) and 0.998 (95% CI 0.997-0.999, P=0.040‖ukb). Increased level of IL-18 was associated with an increased risk of constipation, with ORs of 1.055 (95% CI 1.008-1.104, P=0.022‖Finngene) and 1.001 (95% CI 1.000-1.002, P=0.044‖ukb); while in the Finngene data, the IVW results also suggested that increased levels of IL-2 receptor alpha subunit α and decreased levels of IL-10 and IL-17 were associated with an increased risk of constipation, with ORs of 1.054 (95% CI 1.001-1.110, P=0.049), 0.945 (95% CI 0.896-0.996, P=0.035) and 0.934 (95% CI 0.896-0.997, P=0.040). 【Conclusion】 IL-17 receptor C, IL-18, IL-2 receptor alpha subunit α, IL-10, and IL-17 were causally associated with the risk of constipation.