Expanded Study Diversity Uncovers New Genetic Risk Factors for Inflammatory Bowel Disease

Researchers recently identified new genetic risk factors for inflammatory bowel disease (IBD) by analyzing the genomes of tens of thousands of people from countries in East Asia alongside the genomes of people with ancestry from European countries. The inclusion of people from East Asia significantly expands the diversity of IBD genetic studies and provides insights that will help to understand and predict the disease.

Finding effective treatments for IBD, an umbrella term for Crohn’s disease and ulcerative colitis, has been challenging because it arises from a complicated interaction between genetic and environmental factors, resulting in a disease that varies from person to person. Researchers in the International IBD Genetics Consortium, of which NIDDK’s IBD Genetics Consortium is a member, have been combing through the human genome to find genetic variations (variations in DNA) that increase risk of IBD. By 2022, genetic variations associated with IBD risk had been identified in close to 250 regions of the genome, providing insight into the biology of IBD and opening the door to the development of new treatments. Most of these studies, however, had been with participants from (or with ancestry primarily from) European countries, which limited genetic diversity and likely missed many genetic variations that could play important roles in IBD. (While everyone shares the same genes, and many genetic variations are also shared across ancestries, some genetic variations are more common in specific ancestries than others.)

Recently, researchers expanded the diversity of IBD genetics research by analyzing the genomes of close to 30,000 men and women from China, Japan, and Korea, including people with and without IBD, undertaking the largest IBD genetic analysis of participants from countries in East Asia to date. When the East Asian data were analyzed together with previous studies that included about 370,000 participants with ancestry from European countries, also including people with and without IBD, the researchers identified 81 new regions of the genome associated with the disease, raising the total number of IBD-associated regions to 320. The researchers found that, in general, the amount of IBD risk contributed by genetics was similar between the East Asian and European populations; however, the genetic risk for Crohn’s disease was more influenced by ancestry than that for ulcerative colitis. They also tested whether the combined East Asian and European data would enable a more accurate prediction of IBD risk than the European data alone. Looking at IBD risk in Chinese individuals, the researchers found that the new data improved risk prediction significantly, underscoring the importance of including diverse study participants to improve ways of predicting the probability that any given individual might develop IBD.

In addition to improving risk prediction, increasing the diversity of participants in IBD genetic studies also deepened the understanding of IBD by enabling identification of specific genetic variations that could drive the disease in all people. NIDDK’s IBD Genetics Consortium is currently expanding the diversity of its cohorts further; additional studies could determine exactly how genetic variations may affect IBD development across individuals and whether they could potentially serve as targets for new IBD therapies.