Progress towards identifying inflammatory bowel disease susceptibility genes.
Genomewide searches have identified about a dozen genomic regions potentially containing inflammatory bowel disease (IBD) susceptibility loci. Although some were observed in more than one genome scan or in replication studies, no one locus has been identified in all studies. This apparent lack of consistency is explained by the modest effect of most genetic loci in complex traits and by the modest power and the sampling variance of individual family-based studies. Despite these challenges, the field of IBD genetics found convincing evidence of linkage and, more recently, of genetic sequence variants that are strongly associated with disease. The first example was that of the IBD1 locus on chromosome 16, a linkage region confirmed by a large multicentre study, for which the CARD 15 gene was identified--using independent association strategies-as being a gene contributing to Crohn's disease susceptibility. Despite these advances, a number of questions still remain: (1) What is the best approach to identify the remaining IBD susceptibility loci? (2) How do we prove causality for any given gene or genetic variant? (3) How can we best use this information to obtain an understanding of the biological mechanisms underlying disease susceptibility and to identify useful markers of disease progression and response to therapy?
Rioux
John D
JD
Inflammatory Disease Research, Broad Institute of MIT and Harvard, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139-1561, USA.
D002885:Chromosomes, Human, Pair 16; D002986:Clinical Trials as Topic; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008957:Models, Genetic; D053473:Nod2 Signaling Adaptor Protein
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein