Barbosa Fernanda B, Cagnin Natalia F, Simioni Milena, Farias Allysson A, Torres Fábio R, Molck Miriam C, Araujo Tânia K, Gil-Da-Silva-Lopes Vera L, Donadi Eduardo A, Simões Aguinaldo L
Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, Brazil.
Ann Hum Genet. 2017 Nov;81(6):225-233. doi: 10.1111/ahg.12208. Epub 2017 Sep 11.
Case-control studies are a powerful strategy to identify candidate genes in complex diseases. In admixed populations, association studies can be affected by population stratification, leading to spurious genetic associations. Ancestry informative markers (AIMs) can be used to minimise this effect. The aim of this work was to select a set of AIMs to estimate population stratification in a Brazilian case-control study performed using a genome-wide array. A total of 345 single nucleotide polymorphism (SNP) AIMs, selected from the Cytoscan HD array and based on previously reported panels, was used to discriminate between European, African, and Amerindian populations. These SNP-AIMs were used to infer ancestry in systemic lupus erythematosus (SLE) patients (n = 23) and in healthy subjects (n = 110). Moderate population substructure was observed between SLE and control groups (F 0.0113). Although patients and controls have shown a major European genomic contribution, significant differences in the European (P = 6.47 × 10 ) and African (P = 1.14 × 10 ) ancestries were detected between the two groups. We performed a two-step validation of the 345 SNP-AIMs panel estimating the ancestral contributions using a panel of 12 AIMs and approximately 70K SNPs from the array. Evaluation of population substructure in case-control studies, avoiding spurious genetic associations, can be performed using our panel of 345 SNP-AIMs.
病例对照研究是识别复杂疾病候选基因的有力策略。在混合人群中，关联研究可能会受到群体分层的影响，从而导致虚假的基因关联。祖先信息标记（AIMs）可用于将这种影响降至最低。这项工作的目的是选择一组AIMs，以评估在一项使用全基因组芯片进行的巴西病例对照研究中的群体分层情况。从Cytoscan HD芯片中选取并基于先前报道的面板，共345个单核苷酸多态性（SNP）AIMs被用于区分欧洲、非洲和美洲印第安人群体。这些SNP-AIMs被用于推断系统性红斑狼疮（SLE）患者（n = 23）和健康受试者（n = 110）的祖先。在SLE组和对照组之间观察到中等程度的群体亚结构（F = 0.0113）。尽管患者和对照组都显示出主要的欧洲基因组贡献，但在两组之间检测到欧洲（P = 6.47×10）和非洲（P = 1.14×10）祖先的显著差异。我们使用一组12个AIMs和来自芯片的约70K个SNP对345个SNP-AIMs面板估计祖先贡献进行了两步验证。在病例对照研究中，使用我们的345个SNP-AIMs面板可以评估群体亚结构，避免虚假的基因关联。
