U.S. Department of Health and Human Services

New Crohn’s Disease Gene Variants Identified in Ashkenazi Jewish Population

Scientists have discovered new genetic variants associated with Crohn’s disease (CD) while investigating the Ashkenazi Jewish (AJ) population’s high risk for this disease. The AJ, who are of Eastern and Central European descent, have a two- to four-fold greater risk of developing CD than Europeans of non-Jewish descent. Since the most frequent CD susceptibility variants discovered thus far in the AJ population are similar to those found in non-Jewish populations, those variants do not account for the higher risk for people of AJ heritage. For this study, scientists used new methods and technologies to identify unique genetic variations in this high-risk population. To mine the genetic information of this at-risk group, scientists gathered the largest number of AJ CD cases that has been assembled to date. This was accomplished by combining samples from several previous genome-wide association studies (GWAS), including the NIDDK IBD Genetics Consortium. To confirm the ancestry of the study participants, the researchers used genetic analyses to distinguish AJ ancestry from other populations, including non-Jewish Europeans and other Jewish populations. With additional analysis, the scientists were able to further distinguish AJ participants who had different degrees of AJ heritage—100 percent, 75 percent, or 50 percent, for both separate and combined analyses. The researchers then compared genomic data from AJ individuals with and without CD to identify genetic variants associated with this disease, and also compared genomic data from AJ study participants to data from non-Jewish individuals of European descent. These studies resulted in the discovery of five novel regions associated with CD in the AJ population, and the confirmation of several previously identified variants. The new and confirmed variants account for 11.2 percent of the total genetic variance for CD risk in the AJ population. This research demonstrates the complementary value of genetic studies in the Ashkenazi Jewish and other at-risk populations. The newly defined CD variant regions provide the basis for further studies of the biological pathways responsible for CD and may result in novel treatments.

Kenny EE, Pe’er I, Karban A, et al. A genome-wide scan of Ashkenazi Jewish Crohn’s disease suggests novel 
susceptibility loci. PLoS Genet 8: e1002559, 2012.