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首页> 外文期刊>The Journal of Allergy and Clinical Immunology >Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects
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Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects

机译：全基因组血统协会测试确定了6q14.1上常见的欧洲变异是非洲裔美国人哮喘的危险因素

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Background: Genetic variants that contribute to asthma susceptibility might be present at varying frequencies in different populations, which is an important consideration and advantage for performing genetic association studies in admixed populations. Objective: We sought to identify asthma-associated loci in African American subjects. Methods: We compared local African and European ancestry estimated from dense single nucleotide polymorphism genotype data in African American adults with asthma and nonasthmatic control subjects. Allelic tests of association were performed within the candidate regions identified, correcting for local European admixture. Results: We identified a significant ancestry association peak on chromosome 6q. Allelic tests for association within this region identified a single nucleotide polymorphism (rs1361549) on 6q14.1 that was associated with asthma exclusively in African American subjects with local European admixture (odds ratio, 2.2). The risk allele is common in Europe (42% in the HapMap population of Utah residents with Northern and Western European ancestry from the Centre d'Etude du Polymorphisme Humain collection) but absent in West Africa (0% in the HapMap population of Yorubans in Ibadan, Nigeria), suggesting the allele is present in African American subjects because of recent European admixture. We replicated our findings in Puerto Rican subjects and similarly found that the signal of association is largely specific to subjects who are heterozygous for African and non-African ancestry at 6q14.1. However, we found no evidence for association in European American or Puerto Rican subjects in the absence of local African ancestry, suggesting that the association with asthma at rs1361549 is due to an environmental or genetic interaction. Conclusion: We identified a novel asthma-associated locus that is relevant to admixed populations with African ancestry and highlight the importance of considering local ancestry in genetic association studies of admixed populations.
机译：背景：导致哮喘易感性的遗传变异可能在不同人群中以不同的频率出现，这是在混合人群中进行遗传关联研究的重要考虑因素和优势。目的：我们试图确定非裔美国人受试者中与哮喘相关的基因座。方法：我们比较了根据非洲裔美国人哮喘和非哮喘控制成年人的密集单核苷酸多态性基因型数据估计的非洲和欧洲血统。在确定的候选区域内进行了关联的等位基因测试，以校正当地的欧洲混合物。结果：我们在染色体6q上鉴定到显着的祖先关联峰。在该区域内进行关联的等位基因测试确定了6q14.1上的一个单核苷酸多态性（rs1361549），该多态性仅与患有局部欧洲混合物的非裔美国人受试者中的哮喘有关（比值比为2.2）。风险等位基因在欧洲很常见（在犹他州HapMap人口中有42％的埃特德·杜·多态性中心Humain收集了犹他州居民的北欧和西欧血统），而在西非却没有（在伊巴丹Yorupans的HapMap人口中占0％ （尼日利亚），这表明等位基因存在于非裔美国人受试者中，原因是最近有欧洲人混入。我们在波多黎各人的受试者中复制了我们的发现，并类似地发现，关联信号主要针对6q14.1时非洲和非非洲血统杂合的受试者。但是，在没有当地非洲血统的情况下，我们没有发现与美洲裔或波多黎各人有关联的证据，这表明在rs1361549与哮喘的关联是由于环境或遗传相互作用。结论：我们确定了一种新的与哮喘有关的基因座，与非洲血统的混合人群有关，并强调了在混合血统的遗传关联研究中考虑本地血统的重要性。

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