Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.
Nat Genet. 2011 Jul 31;43(9):887-92. doi: 10.1038/ng.888.
Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.
哮喘是一种常见疾病,其发病风险结构复杂,包括遗传和环境因素。我们对北美 5416 名哮喘患者(病例)和另外 12649 名来自相同族群的欧洲裔美国人、非裔美国人或非裔加勒比裔和拉丁裔个体进行了全基因组关联研究的荟萃分析。我们发现了五个易感位点。其中四个位于先前报道的 17q21 上的位置,靠近 IL1RL1、TSLP 和 IL33,但据我们所知,我们首次报告这些位置与三个族群的哮喘风险相关。此外,我们在 PYHIN1 中确定了一个新的哮喘易感位点,该关联仅存在于非洲血统个体中(P = 3.9×10(-9))。这些结果表明,当调查足够大的样本量时,一些哮喘易感位点在祖先差异方面是稳健的,并且与祖先特异性相关的关联也有助于哮喘的复杂遗传结构。