Causal association between inflammatory bowel disease and IgA nephropathy: A bidirectional two-sample Mendelian randomization study

Mofan Xiao; Yan Ran; Jiayuan Shao; Zhangni Lei; Yuling Chen; Yingchao Li

doi:10.3389/fgene.2022.1002928

Causal association between inflammatory bowel disease and IgA nephropathy: A bidirectional two-sample Mendelian randomization study

Front Genet. 2022 Nov 16:13:1002928. doi: 10.3389/fgene.2022.1002928. eCollection 2022.

Authors

Mofan Xiao¹, Yan Ran², Jiayuan Shao¹, Zhangni Lei¹, Yuling Chen¹, Yingchao Li¹

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

Background: An association between inflammatory bowel disease (IBD) [which includes ulcerative colitis (UC) and Crohn's disease (CD)] and IgA nephropathy (IgAN) has been discovered in observational studies, but the causal relationship is still unknown. The aim of this study was to clarify the causal link between IBD (which includes UC and CD) and IgAN via a two-sample Mendelian randomization (MR) analysis. Methods: Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for analyses and were obtained from the publicly available genome-wide association study (GWAS) summary statistics. Inverse-variance weighting (IVW), Mendelian randomization-Egger (MR-Egger) regression, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and the weighted median were utilized to obtain the results. The MR-PRESSO test and MR-Egger regression were also performed to detect and correct horizontal pleiotropy. The Cochran's Q test and "leave-one-out" analysis were also conducted to assess the stability and reliability of the MR results. Results: This study found that IBD, UC, and CD all had significant positive causal effects on IgAN risk (IBD: OR = 1.58, 95% CI 1.15-2.16, p = 4.53 × 10^-3; UC: OR = 1.55, 95% CI 1.14-2.11, p = 4.88 × 10^-3; CD: OR = 1.57, 95% CI 1.21-2.03, p = 5.97 × 10^-4). No significant horizontal pleiotropic effect was found for the causal association between IBD, UC, CD, and the risk of IgAN. Cochran's Q test identified no evidence of heterogeneity for the IV estimates. The "leave-one-out" sensitivity analysis also revealed that the MR results were robust. Conclusion: The results of this two-sample MR analysis supported that IBD, UC, and CD were causally associated with the risk of IgAN, while there was no sufficient evidence for the causal effect of IgAN on IBD, UC, or CD. Our findings provide theoretical support and a new perspective for the diagnosis and treatment of these two diseases.

Keywords: Crohn’s disease; IgA nephropathy; Mendelian randomization; causality; inflammatory bowel disease; ulcerative colitis.