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Sequencing Data Analysis Finds New Genes, Variants Linked to Crohn's Disease Risk

An analysis of large-scale sequencing data has uncovered a number of genes and rare variants associated with susceptibility to Crohn's disease, according to a report in this week's Nature Genetics. Genome-wide association studies have identified hundreds of loci that contribute to the risk of Crohn's disease and other inflammatory bowel disorders, yet the robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. To complement GWASs in this area, an international team of scientists examined sequencing data from over 30,000 patients with Crohn's disease, along with 80,000 population controls, implicating 10 novel genes involved in the general onset of the disease. The genes, the study's authors write, reiterate the central role of innate and adaptive immune cells, as well as autophagy, in Crohn's disease pathogenesis, and highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation. Overall, the work demonstrates that large-scale exome sequencing can complement GWASs by pinpointing specific genes both indirectly implicated by and not yet observed in the studies.