GENETIC RISK VARIANTS FOR INFLAMMATORY BOWEL DISEASE ARE LESS COMMON IN IMMIGRANT THAN NATIVE-BORN PATIENTS

Abstract INTRODUCTION The etiology of Inflammatory Bowel Disease (IBD) is complex, with a significant genetic component to disease risk and over 200 susceptibility loci described. Less is known about epigenetic and environmental factors that increase IBD risk, though previous studies have shown that patients who immigrate assume local disease risk. Previous work by our group has shown high frequencies of disease-associated variants in several risk genes, with African Americans and second-generation immigrants showing the highest genotypic diversity. We aimed to characterize the genetic burden of IBD risk in our population, as well as disease severity and outcomes by immigration status. METHODS We conducted a retrospective chart review of individuals aged 5-21 diagnosed with biopsy proven IBD at SUNY Downstate Medical Center between 2009-2024. Data collected from the electronic medical record (EMR) consisted of demographics, clinical characteristics, laboratory results and the Prometheus Laboratories SGI panel, which reports genotypes for major IBD risk variants in ATG16L1, ECM1, NKX2-3, and STAT3, as well as outcome measures such as complications, change in therapy, or surgery. RESULTS A total of 25 patients were included, comprising 4 native-born, 4 first-generation immigrants, and 17 second-generation immigrants. Disease-related parameters (Table 1) included were age, BMI percentile and clinical laboratory values at diagnosis (hemoglobin, albumin, sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin). While there were no significant differences between groups via one-way ANOVA, both hemoglobin and CRP trended toward significance. Genetic burden, defined as the total number of variant SNPs present in each patient, was significantly different between groups (p = 0.045). Follow up regression analysis showed that genetic burden is higher in native-born patients than in immigrant patients (p = 0.050). Looking at disease outcomes, we saw that that perianal disease was significantly more prevalent in native-born patients (75%) compared to first- (25%) and second-generation (17.6%) patients via logistic regression (p = 0.037). No significant difference was observed in rates of fistula formation or need for surgery, and no patients developed strictures. Escalation in therapy was required in 75% of native-born, 100% of first-generation, and 53% of second-generation patients. DISCUSSION While we previously showed that genetic risk variants are common in our patient population, we now show that native-born patients with inflammatory bowel disease appear to have a significantly higher genetic burden compared to first- and second-generation immigrant patients. Interestingly, second-generation immigrants also appeared to have less perianal disease and require less frequent escalation in therapy.