International team identifies 21 new genetic risk factors for Crohn...( An international consortium of Crohn...)

An international consortium of Crohn's disease researchers has combined data from three independent studies to identify 21 new genetic variants associated with the inflammatory bowel disorder, bringing the total number of risk factors to 32. Several of these are involved with the immune system's inital response to pathogens, supporting earlier evidence that disruptions in a process called autophagy may lead to the disorder's characteristic immune system overactivity. The report will appear in the journal Nature Genetics and is receiving early online release.

"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," says 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. "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."

In 2007 three separate research teams a North American-based team, involving Daly and colleagues at six other institutions and clinical sites; a U.K. team supported by the Wellcome Trust; and a group of French and Belgian investigators each published genome-wide association studies (GWAS) of Crohn's disease that, combined with earlier studies, brought the total number of Crohn's-associated gene sites to 11. Those explained only a small proportion of the heritability of Crohn's, which affects nearly half a million people in the U.S.

Since the power of any GWAS is limited by the number of samples available for screening, the three teams combined their data through a process called meta-analysis, allowing the comparison of data from more than 3,200 Crohn's patients with more than 4,800 controls. That was supplemented by an analysis of new data from
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