Oral Ulcer Increases Risk Of Autoimmune Glomerulonephritis: Mendelian Randomization Study.

Oral ulcers appeared to be a consequence of shared autoimmune mechanisms with IgAN. This study aims to investigate the causal association between oral ulcer and three types of autoimmune glomerulonephritis (GN), including Immunoglobulin A nephropathy (IgAN), Membranous nephropathy (MN), and Antineutrophil cytoplasmic antibodies GN (ANCA GN), at the genetic level by a bidirectional two-sample Mendelian randomization (MR) analysis. All data come from the publicly released genome-wide association studies (GWAS) statistics. Single nucleotide polymorphisms (SNPs) associated with exposure were quality-controlled using strict screening criteria. The MR analysis between oral ulcer and autoimmune GN was performed by inverse-variance weighted (IVW), MR-Egger and Weighted median (WM) method. IVW and MR-Egger were used for sensitivity analysis. Leave-one-SNP-out analysis was used to identify SNPs with potential impact. IVW, MR-Egger, and WM results revealed that oral ulcer was significantly associated with an increased risk of IgAN (p < 0.05, OR > 1). However, oral ulcer was not causally associated with MN and ANCA GN risk (P > 0.05). The sensitivity analyses showed that there was no heterogeneity or horizontal pleiotropy in our positive findings. This study provides evidence of the causal association between oral ulcer and IgAN risk at the genetic level, which provides novel insights into the genetic research of IgAN. However, large-scale studies are needed to confirm and elucidate the underlying mechanisms of this association.