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 2 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 data set of 1,726 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 3,195 cases and 4,419 controls, followed by replication in an additional 1,088 cases and 845 controls.
Results
The meta-analysis of Korean GWAS identified 1 novel locus for ulcerative colitis at rs76227733 on 10q24 (pcombined = 6.56 × 10 -9) and 2 novel loci for Crohn’s disease (CD) at rs2240751 on 19p13 (pcombined = 3.03 × 10 -8) and rs6936629 in on 6q22 (pcombined = 3.63 × 10 -8). Pathway-based analysis of GWAS data using MAGMA showed that 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 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 suggest the importance of studying the inflammatory bowel disease genetics in diverse populations.
An application of matrix eQTL to billions hypothesis testing to identify expression quantitative trait loci in genome wide association studies of inflammatory bowel disease