Genome-wide association studies (GWASs) have identified hundreds of loci associated with
Crohn's disease (CD). However, as with all complex diseases, robust identification of the
genes dysregulated by noncoding variants typically driving GWAS discoveries has been
challenging. Here, to complement GWASs and better define actionable biological targets,
we analyzed sequence data from more than 30,000 patients with CD and 80,000 population
controls. We directly implicate ten genes in general onset CD for the first time to our …

Results To further advance the interpretation of GWAS loci—and to define novel CD-
associated genes using variation rarer than that routinely detected by GWASs—we pursued
large-scale exome sequencing using CD case and control collections from more than 35
centers in the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The
primary analysis consisted of exome sequencing of 18,816 CD cases across 35 IBD studies
and 13,412 non-IBD control samples from the same studies. These samples were all …