Methods of predicting the need for surgery in crohn's disease

Abstract

The present invention relates to methods of predicting susceptibility to a severe form of Crohn's disease in an individual by determining the presence or absence of one or more risk variants. In one embodiment, the risk variants comprise a combination of genetic risk variants and clinical risk factors. In another embodiment, the genetic risk variants are at the IL12B genetic locus. In another embodiment, the severe form of Crohn's disease is characterized by a rapid progression to a condition requiring surgery for treatment.

What is claimed is: 
     
         1 . A method of diagnosing susceptibility to a severe form of Crohn's disease in an individual, comprising:
 obtaining a sample from the individual;   assaying the sample to determine the presence or absence of one or more risk variants at the IL12B genetic locus; and   diagnosing susceptibility to a severe form of Crohn's disease in the individual based on the presence of one or more risk variants at the IL12B genetic locus.   
     
     
         2 . The method of  claim 1 , wherein the severe form of Crohn's disease is characterized by a rapid progression to a condition requiring surgery for treatment. 
     
     
         3 . The method of  claim 1 , further comprising determining the presence of one or more clinical, serologic and genetic risk factors. 
     
     
         4 . The method of  claim 1 , further comprising determining the presence of anti-ASCA, pANCA, anti-Cbir1, anti-OmpC and/or anti-I2. 
     
     
         5 . The method of  claim 1 , further comprising determining the presence of one or more risk variants at the NDFIP1, C13orf31, SMAD3, 21q21, IBD5, CACNA2D1, ZNRF1, and LDHD genetic loci. 
     
     
         6 . The method of  claim 1 , wherein the one or more risk variants comprise SEQ. ID. NO.: 1. 
     
     
         7 . The method of  claim 1 , wherein the one or more risk variants comprise SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO. 7, and SEQ. ID. NO.: 8. 
     
     
         8 . A method of prognosing Crohn's disease in an individual, comprising:
 determining the presence of a risk variant at the IL12B genetic locus and one or more risk factors in the individual comprising a diagnosis of Crohn's disease in the small bowel location, age of diagnosis, and/or risk serological factors; and   prognosing a severe form of Crohn's disease characterized by a rapid progression to conditions associated with requiring surgery for treatment in the individual based on the presence of a risk variant at the IL12B genetic locus and one or more risk factors in the individual.   
     
     
         9 . The method of  claim 8 , further comprising determining the presence of one or more risk variants at the genetic loci of NDFIP1, C13orf31, SMAD3, 21q21, IBD5, CACNA2D1, ZNRF1, and/or LDHD. 
     
     
         10 . The method of  claim 8 , wherein the risk serological factors comprise anti-ASCA, pANCA, anti-Cbir1, anti-OmpC and/or anti-I2. 
     
     
         11 . The method of  claim 8 , wherein the one or more risk variants comprise SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO. 7, and SEQ. ID. NO.: 8. 
     
     
         12 . A method of treating Crohn's disease in an individual, comprising:
 diagnosing susceptibility to a severe form of Crohn's disease in the individual based on the presence of one or more risk variants at the IL12B genetic locus; and   treating the Crohn's disease in the individual.   
     
     
         13 . The method of  claim 12 , wherein the severe form of Crohn's disease is characterized by a rapid progression to a condition requiring surgery for treatment. 
     
     
         14 . The method of  claim 12 , wherein diagnosing susceptibility to a severe form of Crohn's disease further comprises determining the presence of one or more clinical, serologic and genetic risk factors. 
     
     
         15 . The method of  claim 12 , wherein diagnosing susceptibility to a severe form of Crohn's disease further comprises determining the presence of anti-ASCA, pANCA, anti-Cbir1, anti-OmpC and/or anti-I2. 
     
     
         16 . The method of  claim 12 , wherein diagnosing susceptibility to a severe form of Crohn's disease further comprises determining the presence of one or more risk variants at the NDFIP1, C13orf31, SMAD3, 21q21, IBD5, CACNA2D1, ZNRF1, and LDHD genetic loci. 
     
     
         17 . The method of  claim 12 , wherein the one or more risk variants comprise SEQ. ID. NO.: 1, SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO. 7, and SEQ. ID. NO.: 8.