Although it is well known that the clinical course of immune-mediated disease can vary dramatically between patients, the reasons for this are poorly understood.  

Using Crohn’s disease as an exemplar, James Lee and Daniele Biasci in Ken Smith’s lab (Department of Medicine) investigated whether there may be a genetic contribution to prognosis by comparing the genetic profiles of patients with either particularly mild or particularly aggressive disease. This within-cases GWAS identified genetic variants in several genes that were associated with Crohn’s disease prognosis, but strikingly none of these variants (or genes) had previously been implicated in Crohn’s disease susceptibility. Conversely, none of the 170 disease susceptibility SNPs were found to influence prognosis – either individually or collectively. 

These results, published in Nature Genetics, suggest that the biological pathways that determine prognosis are likely to be distinct from those that drive initial disease development, and could provide new opportunities for therapeutic intervention.