World Congress of Gastroenterology

WCOG 2019


 
PREDICTION OF INFLAMMATORY BOWEL DISEASES BY GENETIC RISK SCORE IN ASIAN GENERAL POPULATIONS
Shifteh Abedian 1 Sunny H.Wong 2 Suzanne Van Sommeren 4 Atsushi Takahashi 5 Jae Hee Cheon 6 Ajit Sood 7 Homayoon Vahedi 3 Keiko Yamazaki 8 Won Ho Kim 6 Thelma B K 9 Nasser E Daryani 10 Michiaki Kubo 8 Suk-Kyun Yang 11 Rupa Banerjee 12 Reza Malekzadeh 3 Rinse . K. Weersma 4 Siew. C. Ng 2 Behrooz .Z . Alizadeh 1

1- DEPARTMENT OF EPIDEMIOLOGY, UNIVERSITY OF GRONINGEN AND UNIVERSITY MEDICAL CENTER GRONINGEN, GRONINGEN, NETHERLANDS
2- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Science, the Chinese University of Hong Kong
3- Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
4- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
5- Laboratory for Statistical Analysis, RIKEN, Yokohama, Japan
6- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
7- Department of Medicine, Dayanand Medical college and Hospital, Ludhiana, India
8- Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan
9- Department of Genetics, University of Delhi South Campus, New Delhi, India
10- Department of Gastroenterology, Emam Hospital, Tehran, Iran
11- Department of Gastroenterology and Hepatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
12- Department of Gastroenterology ,Asian Institute of Gastroenterology, Hyderabad, India
 
Background/Aims:

The clinical implication of genetic findings in Inflammatory Bowel Disease (IBD) is matter of persistent debate especially in Asian population where the prevalence of IBD including Crohns Disease (CD) and Ulcerative Colitis (UC) is rising. We aimed to investigate the predictability of IBD, CD and UC by the means of Genetic Risk Score (GRS) in yet unaffected high risk individuals form East Asia (EA) and Central Asia (CA). We included one of the largest and most accurate collections of Asian population based samples of IBD with genome wide data available to date, based on a prior strong genetic study supplying enrich genetic data to capture IBD probability compared to the Caucasian.

Materials and Methods:

This present study included 9,698 subjects, consisting of 2,003 CD, 2,730 UC and 4,965 country, age and gender-matched controls, genotyped on the Immunochip array of three EA (Japan, South-Korea and China) and two CA countries (India and Iran). We generated a multi-locus GRS for each population by combining information from up to 201 known genome wide significant IBD associated variants to summarize the total load of genetic risk for each phenotype. We estimated explained variance and predictability of IBD, CD and UC by GRS. We shuffled the EA data into: training set including two out of the three EA populations to build a model to calculate odds ratio (OR) for each IBD variants, and a test set including the third population for the validation of predictive model built in the training set. For Indian and Iranian populations, we used the previously estimated ORs for Caucasian population, to build GRS and test the predictive model in these two populations. (Figure )

Results:

GRS of IBD could significantly explain up to 4.40% and 4.14% of IBD variance in EA and CA populations but given a prevalence of 0.01% and 0.04% for IBD it yields to a negligible predictive probability up to 8.8x10-4 and 5.52x10-4. GRS of CD and UC could significantly explain CD and UC to a lesser extent compared to IBD given a lower prevalence of CD and UC. (Figure 2)

Conclusion:

The present study shows that the association of GRS which was built upon combining the effect of genome wide associated risk alleles based on Trans-ethnic analyses are applicable across Asian populations. GRS alone can explain a limited percentage of disease occurrence in Asian general population (<5% of disease susceptibility) and , is unlikely to provide a strong predictive probability of IBD, CD and UC in in the Asian general populations.

Keywords:

Inflammatory bowel disease, Crohn’s Disease, Ulcerative colitis, Genetic risk score (GRS), Explained disease susceptibility, Risk prediction, Risk estimate.