EP294 - Genome-Wide Association Study Identifies Multiple Susceptibility Loci for Inflammatory bowel disease in Taiwan

Purpose/Background: Inflammatory Bowel Disease (IBD) is a long-term, debilitating condition affecting the gastrointestinal tract, encompassing two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Earlier genome-wide association studies uncovered 240 risk loci linked to inflammatory bowel disease. However, there has yet to be a comprehensive and credible large-scale project assessing SNPs for IBD in the Han Chinese population. Thus, our goal was to identify susceptibility loci for IBD by conducting a genome-wide association study (GWAS) using data from the Taiwan Precision Medicine Initiative (TPMI). This study included groups of patients with Crohn's disease (CD) and ulcerative colitis (UC) as the case group, while participants without IBD served as the control group.

Methods/Interventions: The participants included in this study were recruited from Tri-Service General Hospital (TSGH) as part of the Taiwan Precision Medicine Initiative (TPMI). Initially, 62 IBD patients were identified from among the TSGH TPMI participants. The control group consisted of 28540 patients without IBD. To analyze the genotyping data from the TPM array, SNPs with a low typing call rate ( < 80%) were filtered out, and the remaining data was subjected to association analysis using PLINK 1.9 software. Variants with low quality (minor allele frequency less than 0.05 and Hardy-Weinberg equilibrium less than 1 X 10-6) were removed, and highly significant p-values (less than 1 × l0-5) were selected for further analysis.

Results/Outcomes: eight SNPs demonstrated a genome-wide significant association with IBD risk (Table 1). In Crohn's disease (CD), the following SNPs were identified: rs62239894 (C3orf20; LINC02011, OR = 4.05; p = 4.50 × 10⁻⁷), rs7718468 (PRLR, OR = 3.75; p = 7.22 × 10⁻⁷), and rs16944930 (SHISA6, OR = 3.77; p = 3.78 × 10⁻⁷). In ulcerative colitis (UC), rs79571564 (OTOS; GPC1, OR = 4.61; p = 6.89 × 10⁻⁷) and rs75204054 (ABCB5, OR = 3.51; p = 5.86 × 10⁻⁷) were found to be significant. For IBD unclassified (IBDU), rs4312609 (FGF12, OR = 2.88; p = 1.41 × 10⁻⁷), rs151178328 (CCDC169; CCDC169-SOHLH2, OR = 4.56; p = 7.65 × 10⁻⁷), and rs62586066 (ATXN3L; EGFL6, OR = 5.12; p = 8.13 × 10⁻⁷) also showed significant associations.

Conclusion/Discussion: We discovered eight new susceptibility loci in the Han Chinese population that encode proteins involved in pathways recognized as key therapeutic targets for inflammatory bowel disease.

Figure 1
The Manhattan plot for the genome-wide association study (GWAS) of inflammatory bowel disease (IBD) in the Taiwanese population is depicted in Figure 1. The three subplots represent different IBD subtypes: (1a) Crohn’s disease (CD)

Figure 2
resents the GO annotations of variant genes associated with CD (Figure 2a), UC (Figure 2b), and IBDU (Figure 2c), highlighting the various gene functional characterizations. These annotations were selected based on a p-value threshold of < 0.05.