Exploring potential causal genes for mouth ulcers: A Mendelian randomization and transcriptome- wide association analysis

Abstract

Abstract In this study, we explored genes that were pleiotropically associated with mouth ulcers. We adopted the summary data-based Mendelian randomization (SMR) method which estimated the pleiotropic effect of gene expression on mouth ulcers. We performed separate SMR analysis using GTEx and CAGE eQTL data. We also conducted transcriptome-wide association study (TWAS) to explore genes whose cis-regulated expression levels were associated mouth ulcers. Using GTEx eQTL data, the SMR identified 70 probes, with CCR1 (ENSG00000163823.3, PSMR=9.20×10–17), PPP5C (ENSG00000011485.10, PSMR=6.86×10–16) and HLA-DRB5 (ENSG00000198502.5, PSMR=1.54×10–15) being the top three genes. Using the CAGE eQTL data, our SMR analysis identified 137 probes tagging 111 unique genes with CCR3 (ILMN_1763322, PSMR=7.76×10–41), CCR1 (ILMN_1678833, PSMR=3.89×10–38) and CA425595 (ILMN_1725170, PSMR=4.15×10–19) being the top three genes. TWAS analysis identified 181 significant genes whose expression was associated with mouth ulcers, 58 of which were also identified by SMR analysis using GTEx eQTL data and 39 by the SMR analysis using CAGE eQTL data. Our findings highlight the important roles of genes in the CCR family and the HLA complex in the pathogenesis of mouth ulcers. More studies are needed to explore the underlying mechanisms in the etiology of mouth ulcers.