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closeAuthor's summary
Posted by lottaz on 12 Sep 2011 at 10:10 GMT
Our understanding of the genetic contribution in complex diseases, such as inflammatory bowel disease (IBD), has improved thanks to major technical improvements in high-throughput genotyping platforms, which made possible genome-wide analysis of genetic polymorphisms in large multicentric studies enrolling several thousand patients (so-called genome-wide association studies, GWAS). GWAS studies and GWAS meta-analyses revealed many IBD-associated genetic loci. However, these loci typically contain multiple genes, and only few single genes could be identified. In our study, we systematically reviewed all genetic linkage and association studies on populations of European ancestry published in the last 30 years, which served as a basis for a comprehensive evaluation of IBD-associated critical genomic regions. We developed a computer algorithm to map genes of interest onto these critical regions and to generate a list of genes ranked according to the accumulated evidence for their association with disease. We applied this approach to all known protease and protease inhibitor genes and were able to identify several novel candidates among this gene family, several of which could be confirmed in an ongoing replication study. This new approach solves some of the problems encountered when subjectively selecting genes in disease-associated loci for further evaluation.