Data_Sheet_5_Amerindian ancestry proportion as a risk factor for inflammatory bowel diseases: results from a Latin American Andean cohort.xlsx

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.

背景与研究目标
拉丁美洲人群在炎症性肠病（Inflammatory Bowel Diseases, IBD）的遗传学研究中仍存在代表性不足的问题。当前大多数IBD遗传关联研究均以高加索人、非洲人及亚洲人群为研究对象，南美安第斯地区的此类遗传关联尚未得到详细评估。本研究旨在探究已报道的IBD遗传风险变异对智利队列的影响，以及该队列中祖先血统成分对IBD的贡献。

研究方法
本研究共纳入192名智利IBD患者，采用Illumina全球筛查芯片（Illumina Global Screening Array）进行基因分型。将上述基因型数据与3147名智利对照人群的同类基因型数据进行合并。使用ADMIXTURE软件估算艾马拉人、非洲人、欧洲人及马普切人的祖先血统比例。本研究计算了性别、年龄及祖先血统比例的比值比（Odds Ratios, OR）与95%置信区间（Confidence Intervals, CI）。此外，我们还分别以及联合遗传祖先成分，探究了与已报道的IBD风险变异的关联。

研究结果
IBD患者的马普切血统比例的第一和第三四分位数分别为24.7%与34.2%，最低组与最高组相比的比值比为2.30（95%CI：1.52~3.48）。在180个已报道的IBD风险单核苷酸多态性（Single Nucleotide Polymorphism, SNP）中，仅rs7210086这一个变异与智利队列的IBD风险相关（校正后P=0.01），该变异与髓系细胞密切相关。

研究结论
智利人群的美洲原住民血统类型与比例似乎与IBD风险存在关联。本安第斯地区与IBD风险相关的遗传变异与髓系细胞及固有免疫应答相关。