A statistical model accounting for dozens of different genes in combination—and the interactions between them—is an important step forward in understanding the genetic factors affecting the risk of Crohn's disease (CD), reports a study in Inflammatory Bowel Diseases, official journal of the Crohn's & Colitis Foundation of America (CCFA). It's not just how many risk genes are present, but how those genes interact with each other that determines the inheritance of CD risk, suggests the report by a research group from the Cleveland Clinic and the University of Pittsburgh. The study is the first to show that information on genetic interactions can improve the ability to predict CD risk and explain its genetic heritability. CD is a chronic inflammatory bowel disease affecting up to 700,000 Americans. Although the exact cause is unknown, CD appears to result from an "inappropriate persistent immune response." In addition to genetics, microbial and environmental factors likely play important roles in the development of CD. Using modern genetic research methods, called genome-wide association studies (GWAS), researchers have identified at least 71 genes that appear to affect CD risk. However, individual genes have only small effects on CD risk. Even after accounting for the combined effects of CD risk genes, less than one-fourth of CD heritability can be explained. To address this issue, the researchers developed a new model exploring "higher-order genetic interactions" among known CD risk genes. The model was designed to evaluate not only the additive effects of having multiple CD risk genes, but also the possible impact of interactions between genes.
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