Genome wide association (GWA) studies of SNPs are helping scientists learn about the underlying biology of many complex diseases. But even the most enthusiastic proponents of this relatively new type of research admit that many studies simply can’t find genetic variations that have real, but very small, effects. This means information that might be useful for diagnosis, prevention or treatment of a disease is being left on the table. The 23andMe research initiative, 23andWe, is one way of addressing this problem.
Researchers from Children’s Hospital of Philadelphia have devised a different method. Instead of focusing on individual SNPs, they are grouping SNPs together by gene pathway — collections of genes known to work together — and using sophisticated mathematics to identify those groups that appear to be related to disease status.
Using this approach, the researchers have identified the IL12/IL23 pathway — a collection of genes involved in regulating the immune system — as important in Crohn’s disease. Their results, published online today by the American Journal of Human Genetics, not only show the utility of their new method, but may point the way toward the development of new treatments for Crohn’s disease.
“Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies,” the authors write.
The researchers used data from four previous GWA studies for their analysis. Three of the studies were done in people with European ancestry, and the fourth was a small study of African Americans.
“Despite the drastically different association results on the level of individual SNPs across studies, the [IL12/IL23] pathway was consistently picked up as being associated with CD [Crohn’s disease] in all four GWA studies, demonstrating the power and effectiveness of pathway association approach in identifying disease-susceptibility mechanisms,” the author’s write.
It is not completely surprising that the IL12/IL23 pathway was identified as being involved in Crohn’s disease in this study. Several genes from the pathway have previously been linked to Crohn’s disease through GWA studies. Treatments that inhibit the protein encoded by the IL12 gene can reduce symptoms in people with Crohn’s disease, in some cases putting them into complete remission. The authors say that their analysis suggests that more members of this gene pathway — including genes that might never be picked up in a standard GWA study — could also be promising therapeutic targets for the disease.
23andMe customers can learn more in the Crohn’s Disease Clinical Report.