Genome-wide scanning in inflammatory bowel diseases

Inflammatory bowel diseases (IBD) are multifactorial traits involving both environmental and genetic factors. In order to identify the IBD susceptibil ity genes, two groups of strategies have been developed. In the candidate g ene approach, a specific hypothesis is tested by usually investigating the prevalence of specific alleles in groups of affected and control individual s with no familial relationship. Such association studies are powerful and straight-forward. However, they are limited by possible recruitment biases and a multitesting problem due to the large number of possible candidate ge nes. Furthermore, they rely on the existence of a founder effect. In the ge nome scanning searches, no prior assumption is made on the susceptibility g enes. The studies are based on cosegregation (or linkage) analyses performe d on families with several affected members. Their drawbacks are the lack o f statistical power and the low resolution of the localization. Nonetheless , using genome-wide screens, two IBD loci have been localized by several in dependent groups on chromosomes 12 and 16. Additional IBD loci have been pr oposed by individual groups on chromosomes 1, 3, 4, 7, 11, 15 and X. In ord er to gain wide acceptance, the latter localizations are to be confirmed by additional independent studies. Identification of IBD susceptibility genes would represent a key step in the understanding of the pathogenic mechanis m of these diseases. However, in complex disorders, genes are only a part o f the risk factors. Epidemiological studies looking for environmental facto rs are thus complementary of the genetic approach.