Washington: A statistical model that accounts for different genes in combination - and the interactions between them - is an important step in understanding the genetic factors that affect the risk of acquiring Crohn`s disease.
According to the study by a research group from the Cleveland Clinic and University of Pittsburgh, it`s not just how many risk genes are present but how those genes interact with each other that determines the inheritance of Crohn`s disease (CD) risk.
The exact cause for the disease is unknown, but Crohn`s disease 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.
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.
Using data from two large genomewide association studies of CD patients, the model showed `good CD risk predictability.`
People with a higher `cumulative allele score` - reflecting more CD risk genes present - were at higher risk of having CD. However, there wasn`t a major difference in the average total risk score for patients with CD versus healthy people. Based on combinations of risk genes only, the model`s ability to explain genetic inheritance of CD was 24 percent.
But after information of potential interactions between genes were added to the model, explained heritability increased to 27 percent. A model of interactions among five particularly important risk genes was confirmed using an independent patient dataset.
The study has been published in Inflammatory Bowel Diseases, official journal of the Crohn`s and Colitis Foundation of America (CCFA).