GENETIC RISK VARIANTS ARE COMMON IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS FROM MINORITIZED BACKGROUNDS

Abstract INTRODUCTION Inflammatory bowel disease (IBD), comprised of Crohn’s disease (CD) and ulcerative colitis (UC), are chronic immunologically mediated disorders, traditionally thought of as affecting individuals of European and Ashkenazi Jewish heritage. There is a significant genetic component to disease risk, and genome-wide association studies (GWAS) have identified over 200 risk genes. However, most of these studies draw from populations with low numbers of non-Caucasian patients. At our center, the majority of IBD patients are of Afro-Caribbean descent, and many are first- or second-generation immigrants. Although the genetic architecture of IBD in patients of African descent strongly resembles that of Caucasians, some risk alleles are ethnicity specific, and others exert different effect sizes across populations. The frequency and significance of many risk alleles is unknown in our population; thus, we aimed to describe the frequency of a limited number of risk alleles. METHODS We conducted a retrospective chart review of individuals aged 0-21 diagnosed with IBD at SUNY Downstate Medical Center between 2009-2024. Data collected from the electronic medical record (EMR) included demographics, including ethnic background and immigration status (where available), clinical characteristics, disease phenotype, and laboratory results, including the Prometheus Laboratories SGI panel, which reports genotypes for known IBD risk variants in ATG16L1, ECM1, NKX2-3, and STAT3. Pediatric patients with histologically confirmed diagnoses of IBD were included in the study. RESULTS A total of 19 patients met inclusion criteria and had sufficient data available for analysis. Four were native-born Americans (21.1%), 3 first-generation immigrants (15.8%) and 12 second-generation immigrants (63.2%). The majority of patients were African American (10, 52.6%), with 2 Hispanics (10.5%), and 7 from other ethnic backgrounds (36.8%). There were no Caucasian patients (Table1). We noted a high frequency of disease-associated variants in ATG16L1 and STAT3, with less frequency in ECM1 and NKX2-3. Second-generation immigrants exhibited the highest genotypic diversity across all genes, particularly with variants in ATG16L1 and STAT3 (Table 2). African Americans showed the highest genetic diversity, predominantly within the second-generation immigrant group, with significant representation of both ATG16L1 and STAT3 (Table 2). DISCUSSION These genes are widely reported as disease risk alleles for Crohn’s disease in Caucasian and Asian populations. Less is known about the frequency and effect size of these risk alleles in our patient population. Our data shows that they common in patients of African and Caribbean backgrounds, though the degree of effect is unclear. More research is needed to identify the contribution of these markers to genetic risk in non-Caucasian populations.