On adding to the previously identified variants, the total number of risk factors for Crohn's disease has now come to 32.
A large number of these risk factors are also involved with the immune system's initial response to pathogens. This would support earlier evidence that disruptions in a process called autophagy may cause immune system overactivity-the major characteristic of the disorder.
"This greatly increases our knowledge of the genetic architecture of Crohn's and gives us more detailed insight into the biological underpinnings of the disease. Better understanding of the precise functions of these genes and the molecular effects of Crohn's-associated variants should lead us to novel strategies for therapies and, someday, prevention," Nature quoted Mark Daly, PhD, of the Massachusetts General Hospital (MGH) Center for Human Genetic Research and the Broad Institute of MIT and Harvard, the report's senior author, as saying.
In 2007, all the three separate research teams published genome-wide association studies (GWAS) of Crohn's disease that, combined with earlier studies, highlighted a total of 11 Crohn's-associated gene sites, which only explained a small proportion of the heritability of Crohn's.
Due to the limitation of power of any GWAS by the number of samples available for screening, the three teams combined their data through a process called meta-analysis. This enabled them to compare data from more than 3,200 Crohn's patients with more than 4,800 controls. After this, they analysed new data from an additional 3,700 patients and matching controls.
After both the analyses, the 11 previously-identified sites were confirmed and an additional 21 areas associated with susceptibility to Crohn's were found.
Though the newly identified sites may not be as strong as those found in earlier studies, still they may give a clear picture of factors leading to the inappropriate immune-system activation that characterizes the disorder.
"It's amazing that all of the genes indentified in GWAS studies of Crohn's so far align with the pathways that we know are disrupted, systems that sense the presence of microbes and effectively clear them from the body. Mapping the internal circuitry of these systems and identifying the molecular switches that control those circuits should lead to better targeted drugs for Crohn's and other inflammatory bowel diseases." said Ramnik Xavier, MD, of the Center for the Study of Inflammatory Bowel Disease in the MGH Gastroenterology Unit and the MGH Center for Computational and Integrative Biology.
The study will appear in the journal Nature Genetics and is receiving early online release.