Methods of treating refractory inflammatory disease using transcriptomic and genetic risk signatures

A method of treating a Crohn's disease (CD) in a subject comprising administering a therapeutically effective amount of at least one of an inhibitor of phosphodiesterase 4C (PDE4C) activity or expression inhibitor and an agonist of adenylate cyclase 7 (ADCY7) to the subject, provided a risk genotype comprising a single nucleotide polymorphism (SNP) selected from the group consisting of an “A” at rs7958372, a “C” at rs2877453, an “A” at rs71327010, a “C” at rs1169302C, a “G” at rs1169303, an “A” at rs6519183, a “C” at rs685548, an “A” at rs11998187, an “A” at rs531819A, a “G” at rs1041968, a “G” at rs693, an “A” at rs512535, a “G” at rs550619G, an “A” at rs570877, a “G” at rs12713956, an “A” at rs2301723, an “A” at rs2499714, an “A” at rs6583176, an “A” at rs369880, a “G” at rs57884093, an “A” at rs989690, an “A” at rs7704116, an “A” at rs12984273, a “G” at rs16891235, a “C” at rs7296651, an “A” at is rs516535, an “A” at rs9276427, an “A” at rs296564, an “A” at rs296569, an “A” at rs296568, a “G” at rs296567, a “G” at rs296561, a “G” at rs72749142, an “A” at rs9291547, an “A” at rs10761532, an “A” at rs10821813, a “C” at rs1561852, an “A” at rs10994464, a “G” at rs993402, an “A” at rs10994467, an “A” at rs10821822, a “G” at rs1837949, a “C” at rs35597961, a “G” at rs10821830, an “A” at rs975262, an “A” at rs973067, a “G” at rs10509139, an “A” at rs1442539, an “A” at rs2197155, a “G” at rs7919914, a “G” at rs10994476, an “A” at rs35471473, a “G” at rs12785023, a “G” at rs12783716, a “G” at rs10821821, a “G” at rs10994441, a “C” at rs10994442, a “T” at rs10821814, an “A” at rs10994465, a “T” at rs12218617, a “C” at rs10509138, an “A” at rs61854518, a “G” at rs10821699, a “G” at rs7919274, an “A” at rs10761552, a “G” at rs17037425, an “A” at rs2893861, a “C” at rs1993939, a “G” at rs10821833, a “G” at rs1904418, a “G” rs16915196, an “A” at rs61853514, an “A” at rs10994430, an “A” at rs16915231, a “G” at rs2028564, a “G” at rs13196552, an “A” at rs17587597, an “A” at rs17587226, an “A” at rs2276917, an “A” at rs10013653, an “A” at rs11582799, an “A” at rs111692854, and an “A” at rs72632053, is detected in a sample obtained from the subject.

A method of characterizing an inflammatory bowel disease, the method comprising:

• a) obtaining a sample comprising genetic material from a subject having an inflammatory bowel disease;
• b) providing a nucleic acid molecule comprising a detectable moiety, the nucleic acid molecule comprising a nucleic acid sequence that is capable of hybridizing to a risk genotype comprising a single nucleotide polymorphism (SNP) selected from the group consisting of an “A” at rs7958372, a “C” at rs2877453, an “A” at rs71327010, a “C” at rs1169302C, a “G” at rs1169303, an “A” at rs6519183, a “C” at rs685548, an “A” at rs11998187, an “A” at rs531819A, a “G” at rs1041968, a “G” at rs693, an “A” at rs512535, a “G” at rs550619G, an “A” at rs570877, a “G” at rs12713956, an “A” at rs2301723, an “A” at rs2499714, an “A” at rs6583176, an “A” at rs369880, a “G” at rs57884093, an “A” at rs989690, an “A” at rs7704116, an “A” at rs12984273, a “G” at rs16891235, a “C” at rs7296651, an “A” at is rs516535, an “A” at rs9276427, an “A” at rs296564, an “A” at rs296569, an “A” at rs296568, a “G” at rs296567, a “G” at rs296561, a “G” at rs72749142, an “A” at rs9291547, an “A” at rs10761532, an “A” at rs10821813, a “C” at rs1561852, an “A” at rs10994464, a “G” at rs993402, an “A” at rs10994467, an “A” at rs10821822, a “G” at rs1837949, a “C” at rs35597961, a “G” at rs10821830, an “A” at rs975262, an “A” at rs973067, a “G” at rs10509139, an “A” at rs1442539, an “A” at rs2197155, a “G” at rs7919914, a “G” at rs10994476, an “A” at rs35471473, a “G” at rs12785023, a “G” at rs12783716, a “G” at rs10821821, a “G” at rs10994441, a “C” at rs10994442, a “T” at rs10821814, an “A” at rs10994465, a “T” at rs12218617, a “C” at rs10509138, an “A” at rs61854518, a “G” at rs10821699, a “G” at rs7919274, an “A” at rs10761552, a “G” at rs17037425, an “A” at rs2893861, a “C” at rs1993939, a “G” at rs10821833, a “G” at rs1904418, a “G” rs16915196, an “A” at rs61853514, an “A” at rs10994430, an “A” at rs16915231, a “G” at rs2028564, a “G” at rs13196552, an “A” at rs17587597, an “A” at rs17587226, an “A” at rs2276917, an “A” at rs10013653, an “A” at rs11582799, an “A” at rs111692854, and an “A” at rs72632053;
• c) contacting the nucleic acid molecule to the sample obtained from the subject;
• d) detecting a hybridization complex between the nucleic acid molecule and the risk genotype;
• e) characterizing the inflammatory bowel disease as a severe form of Crohn's disease (CD).