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 susceptibility genes, two groups of strategies have been developed. In the candidate gene approach, a specific hypothesis is tested by usually investigating the prevalence of specific alleles in groups of affected and control individuals 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 genes. Furthermore, they rely on the existence of a founder effect. In the genome scanning searches, no prior assumption is made on the susceptibility genes. The studies are based on cosegregation (or linkage) analyses performed on families with several affected members. Their drawbacks are the lack of statistical power and the low resolution of the localization. Nonetheless, using genome-wide screens, two IBD loci have been localized by several independent groups on chromosomes 12 and 16. Additional IBD loci have been proposed by individual groups on chromosomes 1, 3, 4, 7, 11, 15 and X. In order 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 mechanism of these diseases. However, in complex disorders, genes are only a part of the risk factors. Epidemiological studies looking for environmental factors are thus complementary of the genetic approach.