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Science News: New Genetic Risk Factors Identified for Ulcerative Colitis

An international research group, including investigators from the NIDDK’s IBD Genetics Consortium, has identified new genetic risk factors associated with ulcerative colitis (UC) through a genome-wide association study of over 1,000 people with UC compared to other individuals without the disease.

UC causes inflammation in the tissue lining the colon and rectum, which may result from abnormal immune responses within the intestines. Although UC shares some features with the other major form of IBD—Crohn’s disease—other characteristics are distinct. Genome-wide association studies in recent years have identified genetic factors that contribute to each of these forms of IBD. These studies have been particularly fruitful in terms of uncovering genetic regions associated with Crohn’s disease. In the current study, researchers intensified their efforts to identify additional genetic factors that increase susceptibility to UC.

To expand knowledge of genetic contributors to UC, researchers performed a genome-wide association study using DNA collected from individuals with or without UC who shared a similar ancestry, in order to minimize other genetic differences. With this method, they were able to identify chromosomal regions, as well as genes within some of those regions, that are associated with an increased risk of developing UC. Two chromosomal regions were linked for the first time to UC risk. Several genes located within or near these regions play a role in immune function and inflammation, and may contribute to disease susceptibility by altering these processes. Additional genetic factors previously implicated in UC and Crohn’s disease, including the immune system gene IL-23R, were also confirmed in this analysis. However, many genetic factors that had proven important for Crohn’s disease risk were not associated with susceptibility to UC, suggesting that the two forms of IBD have overlapping but unique genetic profiles.

The identification of genetic regions associated with increased susceptibility to UC has the potential to inform understanding of disease processes unique to this form of IBD. Additionally, this knowledge can provide targets for developing new, more personalized therapeutic and preemptive approaches to controlling this disease. 

Silverberg MS, Cho JH, Rioux JD, McGovern DPB, Wu J, Annese V, Achkar JP ,Goyette P, Scott R, Xu W, Barmada MM, Klei L, Daly MJ, Abraham C, Bayless TM, Bossa F, Griffiths AM, Ippoliti AF, Lahaie RG, Latiano A, Paré P, Proctor DD, Regueiro MD, Steinhart AH, Targan SR, Schumm LP, Kistner EO, Lee AT, Gregersen PK, Rotter JI, Brant SR, Taylor KD, Roeder K, and Duerr RH. Ulcerative colitis–risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat Genet 41(2):216-220, 2009.