Crohn’s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD). Although these two forms of IBD share similar clinical and pathological features, there are differences in the disease localization, histopathology, and endoscopic features, suggesting differences in the underlying pathogenic mechanisms of each disease. Understanding the genetic factors that contribute to the disease-specific characteristics is crucial for improving diagnosis and treatment. We performed genome-wide association studies (GWASs) of CD and UC, estimated the proportion of variance explained in CD–UC status and compared the findings to identify genetic loci with divergent effects on CD and UC. In total, we identified 9 genetic loci with divergent effects on CD and UC. Based on polygenic risk score analysis (PRS), we calculated the area under the receiver operating characteristic curve value based on the PRS was 0.74, supporting that the PRS analysis using the CD–UC GWAS has potential to support clinical diagnosis of CD and UC.

Jung S, Kim Y, Park D, Lee Y, Park S, Baek J, Hwang SW, Park SH, Yang SK, Ye BD, Han B, Song K, Lee HS. Case-case genome-wide association analysis identifying genetic loci with divergent effects on Crohn’s disease and ulcerative colitis. Hum Mol Genet. 2023. https://doi.org/10.1093/hmg/ddac241.

Multiple GWASs have suggested that Crohn’s disease (CD) and leprosy might share a common underlying genetic susceptibility. To identify shared susceptibility loci between two diseases in Asians, we first performed a meta-analysis using GWASs of CD in Koreans and leprosy in Chinese populations, and genetic correlation, and pathway analysis. Using these approaches, we identified a novel risk gene for both CD and leprosy, a significant negative genetic correlation, and response to interleukin-18 and regulation of T-helper 1 type immune response as key shared pathways involved in disease pathogenesis.

Jung S, Park D, Lee HS, Kim Y, Baek J, Hwang SW, Park SH, Yang SK, Ye BD, Han B, Sun Y, Liu H, Zhang F, Liu J, Song K. Identification of shared loci associated with both Crohn’s disease and leprosy in East Asians. Hum Mol Genet. 2022. https://doi.org/10.1093/hmg/ddac101.

Large-scale studies on populations of European ancestry have greatly advanced the understanding of IBD-related genetics. Despite the differences in the clinical characteristics of IBD among different ethnicities, the number of studies on non-European populations is limited. To identify novel genetic common variants associated with IBD in Asians, we conducted a GWAS meta-analysis, a recent largest-to-date Asian-specific GWAS of IBD and identified 3 novel susceptibility loci at the genome-wide significance level. Of the 3 novel loci, one novel locus was not replicated in the European data, suggesting the presence of population-specific IBD susceptibility loci.

Jung S, Ye BD, Lee HS, Baek J, Kim G, Park D, Park SH, Yang SK, Han B, Liu J, Song K. Identification of Three Novel Susceptibility Loci for Inflammatory Bowel Disease in Koreans in an Extended Genome-Wide Association Study. J Crohns Colitis. 2021. https://doi.org/10.1093/ecco-jcc/jjab060.

The most recent GWAS on Asian patients with Crohn’s disease (CD) has reported over 20 susceptibility loci, however, there is limited research on integrating genetic variants and eQTL analyses for fine-mapping. To determine the most functionally relevant genes at the genetic loci related to CD in Asians, we established a whole blood eQTL database (http://asan.crohneqtl.com/) from Korean patients with CD and identified 2 target genes based on colocalization analyses using GWAS and eQTL data. Colocalization using the Genotype-Tissue Expression project did not identify one of those target genes, indicating that population-specific eQTL effects exist. Therefore, this eQTL database data highlight the utility of building a population-specific data set, even of modest sample size.

Jung S, Liu W, Baek J, Moon JW, Ye BD, Lee HS, Park SH, Yang SK, Han B, Liu J, Song K. Expression Quantitative Trait Loci (eQTL) Mapping in Korean Patients With Crohn’s Disease and Identification of Potential Causal Genes Through Integration With Disease Associations. Front Genet. 2020. https://doi.org/10.3389/fgene.2020.00486.