High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12

Epidemiological studies have shown that genetic factors contribute to the p athogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn dise ase (CD) and ulcerative colitis (UC). Recent genome scans and replication s tudies have identified replicated linkage between CD and a locus on chromos ome 16 (the IBD1 locus), replicated linkage between IBD (especially UC) and a focus on chromosome 12q (the IBD2 locus), and replicated linkage between IBD (especially CD) and a locus on chromosome 6p (the IBD3 locus). Since t he estimated locus-specific lambda(s) values for the regions of replicated linkage do not account for the overall lambda(s) in CD, and since the publi shed genome scans in IBD show at least nominal evidence for linkage to regi ons on all but two chromosomes, we performed an independent genome scan usi ng 751 microsatellite loci in 127 CD-affected relative pairs from 62 famili es. Single-point nonparametric linkage analysis using the GENEHUNTER-PLUS p rogram shows evidence for linkage to the adjacent D14S261 and D14S283 loci on chromosome 14q11-12 (LOD = 3.00 and 1.70, respectively), and the maximal multipoint LOD score is observed at D14S261 (LOD = 3.60). In the multipoin t analysis, nominal evidence for linkage (P < .05) is observed near D2S117 (LOD = 1.25), near D3S3045 (LOD = 1.31), between D7S40 and D7S648 (LOD = 0. 91), and near D18S61 (LOD = 1.15). Our finding of significant linkage to D1 4S261 and the finding of suggestive linkage to the same locus in an indepen dent study (multipoint LOD = 2.8) satisfies criteria for confirmed linkage, so we propose that the region of interest on chromosome 14q11-12 should be designated the IBD4 locus.