Variants of tnfsf15 and dcr3 associated with crohn's disease

Abstract

Described herein are methods and compositions related to the discovery of associations in TNFSF15 15 and DcR3 genetic loci across in Caucasian, Puerto Rican, and Korean Crohn's Disease, as demonstrated via trans-ethnic fine mapping. The present invention provides methods of quantifying risk and diagnosing susceptibility to Crohn's disease in a subject by determining the presence of one or more risk variants are at the TNFSF15 (or TL1A) and/or DcR3 genetic loci.

What is claimed is: 
     
         1 . A method of treating an inflammatory bowel disease in a subject in need thereof, the method comprising administering to the subject an anti-TL1A antibody, provided that the subject comprises a polymorphism in TNFSF15 at the position “N” within SEQ ID NO: 3, SEQ ID NO: 2, SEQ ID NO: 4, or a combination thereof. 
     
     
         2 . The method of  claim 1 , provided that the inflammatory bowel disease comprises Crohn's disease. 
     
     
         3 . The method of  claim 1 , provided that the subject further comprises a polymorphism in TNFSF15 within rs4979462. 
     
     
         4 . The method of  claim 1 , provided that the subject is of Asian descent. 
     
     
         5 . The method of  claim 1 , provided that the subject further comprises a polymorphism in TNFSF15 within rs7848647, rs6478109, rs59418409, rs7869487, rs6478108, rs10114470, rs3810936, rs4246905, rs4574921, or a combination thereof. 
     
     
         6 . The method of  claim 1 , provided that the subject further comprises a polymorphism in DcR3 within rs6062496, rs1291206, rs1291205, rs2236507, rs2236508, rs6011033, rs55765053, rs34412639, rs2738788, rs2738787, rs1291208, rs74506932, rs80132799, or a combination thereof. 
     
     
         7 . A method of treating an inflammatory bowel disease in a subject in need thereof, the method comprising administering to the subject an anti-TL1A antibody, provided that the subject comprises a polymorphism in TNFSF15 at the position “N” within SEQ ID NO: 12. 
     
     
         8 . The method of  claim 7 , provided that the polymorphism is an insertion. 
     
     
         9 . The method of  claim 7 , provided that the inflammatory bowel disease comprises Crohn's disease. 
     
     
         10 . The method of  claim 7 , provided that the subject further comprises a polymorphism in TNFSF15 within rs7848647, rs6478109, rs7869487, rs6478108, rs10114470, rs3810936, rs4246905, rs4574921, or a combination thereof. 
     
     
         11 . The method of  claim 10 , provided that the subject comprises the polymorphism within rs6478109. 
     
     
         12 . The method of  claim 10 , provided that the subject comprises the polymorphism within rs7848647. 
     
     
         13 . The method of  claim 10 , provided that the subject comprises the polymorphism within rs7869487. 
     
     
         14 . The method of  claim 7 , provided that the subject further comprises a polymorphism in TNFSF15 within rs1322057, rs55768522, rs76779588, rs4979462, or a combination thereof. 
     
     
         15 . The method of  claim 7 , provided that the subject further comprises a polymorphism in DcR3 within rs6062496, rs1291206, rs1291205, rs2236507, rs2236508, rs6011033, rs55765053, rs34412639, rs2738788, rs2738787, rs1291208, rs74506932, rs80132799, or a combination thereof. 
     
     
         16 . A method of treating an inflammatory bowel disease in a subject in need thereof, the method comprising administering to the subject an anti-TL1A antibody, provided that the subject comprises a polymorphism in DcR3 at the position “N” within SEQ ID NO: 17, SEQ ID NO: 14, SEQ ID NO: 20, SEQ ID NO: 18, or a combination thereof. 
     
     
         17 . The method of  claim 16 , provided that the inflammatory bowel disease comprises Crohn's disease. 
     
     
         18 . The method of  claim 16 , provided that the subject further comprises a polymorphism in DcR3 within rs6062496, rs1291206, rs1291205, rs2236508, rs34412639, rs2738788, rs2738787, rs1291208, rs80132799, or a combination thereof. 
     
     
         19 . The method of  claim 16 , provided that the subject further comprises a polymorphism in TNFSF15 within rs7848647, rs6478109, rs59418409, rs7869487, rs6478108, rs10114470, rs3810936, rs4246905, rs4574921, or a combination thereof. 
     
     
         20 . The method of  claim 16 , provided that the subject further comprises a polymorphism in TNFSF15 within rs1322057, rs55768522, rs76779588, rs4979462, or a combination thereof.