Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort

Peer reviewed: TrueAcknowledgements: The authors are indebted to Dr. Justo Lorenzo-Bermejo and collaborators from his group, Dr. Linda Zollner, Dr. Carol Barahona Ponce, Dr. Felix Boekstegers, and EULAT Eradicate GBC, for sharing the genotypic and sociodemographic information from control individuals as well as providing expert advice on statistical analysis. This study and its research would not have been possible without the exceptional support of the patients, nurses, technicians, and medical scheduler from the Endoscopy Unit of the Hospital San Borja Arriarán, Santiago, Chile.Background and aimsLatin American populations remain underrepresented in genetic studies of inflammatory bowel diseases (IBDs). Most genetic association studies of IBD rely on Caucasian, African, and Asian individuals. These associations have yet to be evaluated in detail in the Andean region of South America. We explored the contribution of IBD-reported genetic risk variants to a Chilean cohort and the ancestry contribution to IBD in this cohort.MethodsA total of 192 Chilean IBD patients were genotyped using Illumina's Global Screening Array. Genotype data were combined with similar information from 3,147 Chilean controls. The proportions of Aymara, African, European, and Mapuche ancestries were estimated using the software ADMIXTURE. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for gender, age, and ancestry proportions. We also explored associations with previously reported IBD-risk variants independently and in conjunction with genetic ancestry.ResultsThe first and third quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7 and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52–3.48) for the lowest vs. the highest group. Only one variant (rs7210086) of the 180 reported IBD-risk SNPs was associated with IBD risk in the Chilean cohort (adjusted P = 0.01). This variant is related to myeloid cells.ConclusionThe type and proportion of Native American ancestry in Chileans seem to be associated with IBD risk. Variants associated with IBD risk in this Andean region were related to myeloid cells and the innate immune response.