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Dozens of Genes Linked to Bowel Diseases

Article / Review by on November 19, 2012 – 6:08 pmNo Comments

Dozens of Genes Linked to Bowel Diseases

Researchers found 71 new human genes associated with Crohn’s disease and ulcerative colitis—forms of chronic inflammatory bowel disease (IBD) that affect nearly 2.5 million people worldwide. The study brings the total number of genes linked with IBD to 163.

Dozens of Genes Linked to Bowel Diseases

The most common signs of IBD are diarrhea and abdominal pain. Its exact causes are unclear. Researchers believe an unknown factor or agent triggers an abnormal reaction by the body’s immune system. Genes play some role, as the disease tends to run in families. People of Jewish heritage, particularly Ashkenazi Jews of Eastern European descent, have an increased risk of developing IBD.

A consortium of researchers from the United States, Canada and Europe set out to find common genetic variants that influence the risk for IBD. They did a meta-analysis of 15 previous genome-wide association studies. Led by Dr. Judy H. Cho of Yale School of Medicine, their analysis included data from more than 6,000 people with Crohn’s disease, 7,000 with ulcerative colitis and 35,000 unaffected people.

The scientists also analyzed DNA samples using a custom chip called the Immunochip. This chip includes almost 200,000 small genetic variations selected from past studies of autoimmune and inflammatory diseases. The team examined more than 60,000 samples from over 20,000 people with Crohn’s disease, 15,000 people with ulcerative colitis, and 25,000 people with neither disease. The study was partly funded by several NIH institutes, led by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results appeared in the November 1, 2012, issue of Nature.

The scientists found 71 new genes associated with IBD. Of the 163 genes now linked to IBD, 110 are associated with Crohn’s disease and ulcerative colitis, 30 are specific to Crohn’s and 23 are specific to ulcerative colitis. For 134 of the genes, the variants associated with disease aren’t predicted to cause changes in protein structure. These variants may affect when and to what extent the genes are turned on and off, known as gene expression.

The team found that many of the genes tied to IBD were previously linked with other inflammatory diseases, such as ankylosing spondylitis (spine inflammation) and the skin disorder psoriasis. “Performing the meta-analysis on these large datasets provides the statistical power and integrity to confirm the associations of these genes to IBD and identifies gene variants that until now, were only suspected to overlap with other inflammatory diseases,” Cho says.

The researchers also found considerable overlap between the genes linked to IBD and those responsible for resisting infections by mycobacteria, which can cause diseases such as tuberculosis and leprosy. “The marked extent to which the findings make clear the overlap between IBD and mycobacterial infections was rather unexpected,” Cho says.

These findings will help investigators further explore the pathways that lead to IBD and other inflammatory diseases. This knowledge may help lead to better, more targeted treatments. Nevertheless, even this large number of genes explains only a fraction of the risk for IBD. Further study will be needed to reveal other factors involved, both genetic and environmental.

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*  The above story is reprinted from materials provided by National Institutes of Health (NIH)
** The National Institutes of Health (NIH) , a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency—making important discoveries that improve health and save lives. The National Institutes of Health is made up of 27 different components called Institutes and Centers. Each has its own specific research agenda. All but three of these components receive their funding directly from Congress, and administrate their own budgets.

More about National Institutes of Health (NIH)

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