Identification of Three Novel Susceptibility Loci for Inflammatory Bowel Disease in Koreans in an Extended Genome-Wide Association Study

Abstract

Background and Aims: Genome-wide association studies [GWAS] of inflammatory bowel disease [IBD] in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify two new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional dataset of 1726 cases and 378 controls. Methods: An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3195 cases and 4419 controls, followed by replication in an additional 1088 cases and 845 controls. Results: The meta-analysis of Korean GWAS identified one novel locus for ulcerative colitis at rs76227733 on 10q24 [p(combined) = 6.56 x 10(-9)] and two novel loci for Crohn's disease [CD] at rs2240751 on 19p13 [p(combined) = 3.03 x 10(-8)] and rs6936629 on 6q22 [p(combined) = 3.63 x 10(-8)]. Pathway-based analysis of GWAS data using MAGMA showed that the MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14% of the variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population. Conclusions: The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations.