The Paradoxical Influence of Amerindian Ancestry on Clinical Outcomes in Crohn’s Disease and Ulcerative Colitis: Insights from a Chilean Cohort.

Abstract

Background. 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. Methods. 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 employed statistical tests to compare the different groups. Results. The median distribution of global ancestry was 58% European, 39% Amerindian, and 2% African. There were no significant differences in IBD risk based on ancestry proportion between cases and controls. Ulcerative colitis (UC) patients diagnosed before age 40 had a higher median Amerindian ancestry proportion (39.9% versus 37.4%, P value = 0.01). Conversely, UC patients with prolonged clinical and endoscopy remission had a lower median Amerindian ancestry proportion (35% versus 39%, P value = 0.02). 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). Only 6% of patients with resective surgery had a higher Amerindian ancestry proportion. Conclusion. 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.