Vergara Candelaria, Caraballo Luis, Mercado Dilia, Jimenez Silvia, Rojas Winston, Rafaels Nicholas, Hand Tracey, Campbell Monica, Tsai Yuhjung J, Gao Li, Duque Constanza, Lopez Sergio, Bedoya Gabriel, Ruiz-Linares Andrés, Barnes Kathleen C
Institute for Immunological Research, University of Cartagena, Bolívar, Colombia.
Hum Genet. 2009 Jun;125(5-6):565-79. doi: 10.1007/s00439-009-0649-2. Epub 2009 Mar 17.
African descended populations exhibit an increased prevalence of asthma and allergies compared to Europeans. One approach to distinguish between environmental and genetic explanations for this difference is to study relationships of asthma risk to individual admixture. We aimed to determine the admixture proportions of a case-control sample from the Caribbean Coast of Colombia currently participating in genetic studies for asthma, and to test for population stratification and association between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 368 asthmatics and 365 non-asthmatics for 52 autosomal ancestry informative markers, six mtDNA haplogroups and nine haplogroups and five microsatellites in Y chromosome. Autosomal admixture proportions, population stratification, and associations between ancestry and the phenotypes were estimated by ADMIXMAP. The average admixture proportions among asthmatics were 42.8% European, 39.9% African and 17.2% Native American and among non-asthmatics they were 44.2% (P = 0.068), 37.6% (P = 0.007) and 18.1% (P = 0.050), respectively. In the total sample, the paternal contributions were 71% European, 25% African and 4.0% Native American and the maternal lineages were 56.8% Native American, and 20.2% African; 22.9% of the individuals carried other non-Native American mtDNA haplogroups. African ancestry was significantly associated with asthma (OR: 2.97; 95% CI: 1.08-8.08), high tIgE (OR: 1.9; 95% CI: 1.17-3.12) and socioeconomic status (OR = 0.64; 95% CI: 0.47-0.87). Significant population stratification was observed in this sample. Our findings indicate that genetic factors can explain the association between asthma and African ancestry and suggest that this sample is a useful resource for performing admixture mapping for asthma.
与欧洲人相比,非洲裔人群哮喘和过敏的患病率更高。区分这种差异的环境和遗传解释的一种方法是研究哮喘风险与个体混合比例之间的关系。我们旨在确定目前参与哮喘基因研究的哥伦比亚加勒比海岸病例对照样本的混合比例,并测试人群分层以及非洲血统与哮喘和总血清IgE水平(tIgE)之间的关联。我们对368名哮喘患者和365名非哮喘患者进行了52个常染色体血统信息标记、六个线粒体DNA单倍群、九个单倍群以及Y染色体上五个微卫星的基因分型。通过ADMIXMAP估计常染色体混合比例、人群分层以及血统与表型之间的关联。哮喘患者中欧洲人、非洲人和美洲原住民的平均混合比例分别为42.8%、39.9%和17.2%,非哮喘患者中分别为44.2%(P = 0.068)、37.6%(P = 0.007)和18.1%(P = 0.050)。在整个样本中,父系贡献为71%欧洲人、25%非洲人和4.0%美洲原住民,母系血统为56.8%美洲原住民和20.2%非洲人;22.9%的个体携带其他非美洲原住民线粒体DNA单倍群。非洲血统与哮喘(OR:2.97;95% CI:1.08 - 8.08)、高tIgE(OR:1.9;95% CI:1.17 - 3.12)和社会经济地位(OR = 0.64;95% CI:0.47 - 0.87)显著相关。在该样本中观察到显著的人群分层。我们的研究结果表明,遗传因素可以解释哮喘与非洲血统之间的关联,并表明该样本是进行哮喘混合图谱研究的有用资源。