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

Abstract

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; OR_{weighted median} = 1.028, P = 0.049; OR_{weighted mode} = 1.030, p = 0.044). Furthermore, we observed a causal link between celiac disease and a decreased eGFRcrea (OR_IVW = 0.997, P = 2.94E-06; OR_{weighted median} = 0.996, P = 1.68E-05; OR_{weighted mode} = 0.996, P = 3.11E-04; OR_{MR 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.

Keywords:

• Celiac disease
• chronic kidney disease
• estimated glomerular filtration rate
• Mendelian randomization
• causal relationship

Authors’ contributions

Z.C and Y.X. designed research. Z.C, Z.Z, B.J, and Y.X. analyzed the data. Z.C wrote the draft manuscript. Y.X. supervised the research and performed writing-review and editing. All authors verified the data and approved the final version of the manuscript.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

The data underlying this article were accessed from the IEU OpenGWAS consortium (https://gwas.mrcieu.ac.uk/).

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 82070720), Young and Middle-aged Scientific Research Major Project of Fujian Provincial Health Commission (No. 2021ZQNZD004), Joint Funds for the innovation of science and Technology of Fujian province (2019Y9019).