Prediction of Inflammatory Bowel Diseases using Genetic Risk Score in Asian populations

Abstract Background and Aims: The incidence of Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and Ulcerative colitis (UC), is rising in Asian populations. We undertook a cross-population study to explore whether genetic risk scores (GRS) of IBD, CD and UC could explain their occurrence, and whether they can be used to predict disease occurrence in general populations from East Asia (EA) and Central Asia (CA). Methods We studied 9,698 subjects – 4,733 IBD patients (2,003 CD; 2,730 UC) and 4,965 matched controls – who had been genotyped using Immunochip. The subjects were from three East Asian (Japan, South Korea and China) and two Central Asian populations (India and Iran). We generated GRS for each population by combining information from up to 201 genome-wide significant IBD-associated variants to summarize the total load of genetic risk for each phenotype. We then estimated the explained variance and predictability of IBD using the GRS. Results IBD GRS could explain up to 4.40% and 4.14% of IBD variance at a significant level in East Asian and Central Asian populations, respectively, but, given a prevalence of 0.01% and 0.04% for IBD, these yield limited predictive probability. GRS for CD and UC separately proved less significant than GRS for IBD. Conclusion GRS alone can explain only a limited percentage of disease occurrence (< 5% of disease susceptibility) and cannot be used to predict IBD in Asian populations at this time. Our results highlight the significant missing heritability, which may be due to genetic epistasis, gene-environment interactions, or rare variants.