PHG Foundation | Crohn's susceptibility loci increase in number

Crohn's susceptibility loci increase in number
Analysis of a study published in a science journal | By Dr Gurdeep Sagoo | Published 26 November 2010

Study: Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
By: Franke A. et al. (96 authors total)
In: Nature Genetics
Link: http://dx.doi.org/10.1038/ng.717

What this study set out to do:
With 32 known Crohn’s susceptibility loci in 2008, this consortium set out to identify additional disease susceptibility loci.

How they went about it:
The consortium meta-analysed data from six previous Crohn’s disease genome-wide association studies involving over 6,000 cases and 15,000 controls. Promising results were followed up in a further 15,000 cases and 14,000 controls as well as over 400 parent-child trios. Additional analyses were conducted in order to identify candidate genes in the novel susceptibility regions.

Outcome:
Promising findings from the meta-analysis of the published GWAS were followed up in additional cases and controls leading to the identification of 39 susceptibility loci of which 30 were new. 17 biologically interesting genes were identified and have been highlighted for further follow up. The 32 previously identified susceptibility loci were also confirmed.

Conclusion:
This current study has doubled the number of Crohn’s disease susceptibility loci with many potential casual genes identified for additional functional studies. These additional susceptibility loci increase the explained genetic heritability from 20 percent to 23.2 percent. Further work is already underway and promises to further elucidate the pathogenic mechanism of Crohn’s.

Our view:
The authors note that because tagging SNPs act as imperfect proxies for causal SNPs with true disease risk being underestimated, this in turn leads to the proportion of heritability explained also being vastly underestimated. It will be interesting to see how this will be overcome by using new rapid sequencing techniques to aid the understanding of disease genetic aetiology
PHG Foundation | Crohn's susceptibility loci increase in number