Impact of Amerindian ancestry on clinical outcomes in Crohn’s disease and ulcerative colitis in a Latino population

Research in Inflammatory Bowel Disease (IBD) assessing the genetic structure and its association with IBD phenotypes is needed, especially in IBD-underrepresented populations such as the South American IBD population. Aim. We examine the correlation between Amerindian ancestry and IBD phenotypes within a South American cohort and investigate the association between previously identified IBD risk variants and phenotypes. We assessed the ancestral structure (IBD = 291, Controls = 51) to examine the association between Amerindian ancestry (AMR) and IBD variables. Additionally, we analyzed the influence of known IBD genetic risk factors on disease outcomes. We used Chi-square and Fisher's tests to analyze the relationship between phenotypes and ancestry proportions, calculating odds ratios (OR) and confidence intervals (CI). Logistic regression examined genetic variants associations with IBD outcomes, and classification models for predicting prolonged remission were developed using decision tree and random forest techniques. The median distribution of global ancestry was 58% European, 39% Amerindian, and 3% African. There were no significant differences in IBD risk based on ancestry proportion between cases and controls. In Ulcerative colitis (UC), patients with a high Amerindian Ancestry Proportion (HAAP) were significantly linked to increased chances of resective surgery (OR = 4.27, CI = 1.41-12.94, p = 0.01), pouch formation (OR = 7.47, CI = 1.86-30.1, p = 0.003), and IBD reactivation during COVID-19 infection (OR = 5.16, CI = 1.61-6.53, p = 0.005). Whereas, in the Crohn's Disease (CD) group, the median Amerindian ancestry proportion was lower in the group with perianal disease (33.5% versus 39.5%, P value = 0.03). CD patients with High Amerindian Ancestry proportion had lower risk for surgery (OR = 0.17, CI = 0.03-0.83, P value = 0.02). Our study highlights the impact of Amerindian ancestry on IBD phenotypes, suggesting a role for genetic and ancestral factors in disease phenotype. Further investigation is needed to unravel the underlying mechanisms driving these associations.