Genetic association between celiac disease and chronic kidney disease: a two-sample Mendelian randomization study.

OBJECTIVE

A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal impact of celiac disease on the risk of chronic kidney disease (CKD).

METHODS

The study comprised data from three genome-wide association studies involving individuals of European ancestry. The study groups included participants with celiac disease (n = 24,269), CKD (n = 117,165), and estimated glomerular filtration rate levels based on serum creatinine (eGFRcrea, n = 133,413). We employed four widely recognized causal inference algorithms: MR-Egger, inverse variance weighted (IVW), weighted median, and weighted mode. To address potential issues related to pleiotropy and overall effects, MR-Egger regression and the MR-PRESSO global test were performed. Heterogeneity was assessed using Cochran's Q test.

RESULTS

We identified 14 genetic variants with genome-wide significance. The MR analysis provided consistent evidence across the various methodologies, supporting a causal relationship between celiac disease and an elevated risk of CKD (odds ratio (OR)IVW = 1.027, p = 0.025; ORweighted median = 1.028, P = 0.049; ORweighted mode = 1.030, p = 0.044). Furthermore, we observed a causal link between celiac disease and a decreased eGFRcrea (ORIVW = 0.997, P = 2.94E-06; ORweighted median = 0.996, P = 1.68E-05; ORweighted mode = 0.996, P = 3.11E-04; ORMR Egger = 0.996, P = 5.00E-03). We found no significant evidence of horizontal pleiotropy, heterogeneity, or bias based on MR-Egger regression, MR-PRESSO, and Cochran's Q test.

CONCLUSION

The results of this study indicate a causal relationship between celiac disease and an increased risk of CKD.