Novel Associations Between Genome-Wide Single Nucleotide Polymorphisms and MR Enterography Features in Crohn's Disease Patients

Abstract

Background: Patient genetic polymorphism is associated with Crohn's clinical behavior; however, its association with magnetic resonance enterography (MRE) imaging appearance is not known.

Purpose: To analyze a set of known Crohn's disease (CD)-related single nucleotide polymorphisms for associations with MRE imaging phenotype and frequency of imaging.

Study type: Retrospective.

Population: 54 patients (mean age 40 years; 32 females and 22 males) with established CD from 2009 to 2016 who underwent baseline MRE and genetic testing for the presence of 168 single nucleotide polymorphisms (SNPs) potentially associated with inflammatory bowel disease.

Field strength/sequence: 1.5T or 3T clinical scanners, standard MRE clinical pulse sequences, including T₂ -weighted single-shot fast spin echo, balanced steady-state free precession, T₂ -weighted fast spin echo fat-suppressed, and T₁ -weighted fat-suppressed pre- and postcontrast imaging.

Assessment: Three readers (all body imaging fellowship-trained radiologists) independently evaluated all imaging for the presence or absence of active disease and penetrating complications. Date of onset and frequency of endoscopies and cross-sectional imaging (CSI) were recorded. Disease behavior and distribution were categorized according to the Vienna and Montreal classifications, respectively.

Statistical tests: Student's t-test and Fisher's exact test were used to assess significance of continuous and categorical variables, respectively. A hidden Markov model statistical knockoff approach was also applied for the analysis of genetic-imaging associations, with corrected P < 0.05 considered significant.

Results: MRE demonstrated active bowel inflammation in 42 (78%) patients, strictures in 13 (28%), and fistulae in 13 (28%). The SNP rs1292053 (RBS6KB1) was highly associated with small bowel inflammation and luminal narrowing, with observed frequencies of association 0.66 and 0.39, respectively (P = 0.001). rs6062504 (Decoy receptor 3) was associated with lower age of onset (P = 0.012), higher proportion of early disease onset patients (P = 0.012), and higher average number of CSI/year (P = 0.014).

Data conclusion: This study demonstrated significant associations between CD genotype and MRE phenotype and frequency of cross-sectional imaging.

Level of evidence: 3 TECHNICAL EFFICACY STAGE: 2.

Keywords: inflammatory bowel disease; magnetic resonance enterography; radiogenomics; single nucleotide polymorphism.