Refinement in localization and identification of gene regions associated with Crohn disease

Abstract

The risk of Crohn disease (CD) has a large genetic component. A recent meta-analysis of 6 genome-wide association studies reported 71 chromosomal intervals but does not account for all of the known genetic contribution. Here, we refine localization of the previously reported intervals and also identify additional CD susceptibility genes using a mapping approach that localizes causal variants based on genetic maps in linkage disequilibrium units (LDU maps). Using 2 of the 6 cohorts, 66 of the 71 previously reported loci are confirmed and more precise location estimates for these intervals are given. We identify 78 additional gene regions that pass genome-wide significance, providing strong evidence for 144 genes. Additionally, 56 nominally significant signals, but with more stringent and precise colocalization, are identified. In total, we provide evidence for 200 gene regions confirming that CD is truly multifactorial and complex in nature. Many identified genes have functions that are compatible with involvement in immune/inflammatory processes and seem to have a large effect in individuals with extra ileal as well as ileal inflammation. The precise locations and the evidence that some genes reflect phenotypic subgroups will help identify functional variants and will lead to greater insight of CD etiology.