Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Clin Exp Allergy. 2012 Dec;42(12):1724-33. doi: 10.1111/cea.12000.
Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL3, PDE4D, HLA-DQ, and TLE4) via genome-wide association studies.
To identify genetic variants associated with asthma affection status using genome-wide association data.
We describe results from a genome-wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms (SNPs).
The genome-wide association study resulted in the prioritization of 33 variants for immediate follow-up in a multi-staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA-DQA1 (chromosome 6p21.3) was associated with asthma in adults (P-value = 2.2E-08) with consistent evidence in the more heterogeneous group of adults and children (P-value = 1.0E-04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations.
Overall, our findings further replicate the HLA-DQ region in the pathogenesis of asthma. HLA-DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA-DRA, HLA-DQB1 and HLA-DQA2.
哮喘是一种常见的儿童和成人慢性呼吸道疾病。长期以来，人们已经认识到哮喘易感性的一个重要遗传因素，最近通过全基因组关联研究鉴定了几个基因（例如 ORMDL3、PDE4D、HLA-DQ 和 TLE4）。
利用全基因组关联数据鉴定与哮喘发病状态相关的遗传变异。
我们描述了在 3855 名受试者中进行的一项基于全基因组关联的哮喘研究结果，该研究使用了 455089 个单核苷酸多态性（SNP）的面板。
全基因组关联研究优先考虑了 33 个变异，以便在多阶段复制工作中进行后续研究。其中，位于 HLA-DQA1（6p21.3 号染色体）内 1kb 内的常见多态性（rs9272346）与成人哮喘相关（P 值=2.2E-08），在成人和儿童更为混杂的群体中也有一致的证据（P 值=1.0E-04）。此外，我们人群中一些先前的哮喘全基因组关联研究中鉴定的基因与哮喘呈名义相关。
总的来说，我们的研究结果进一步复制了 HLA-DQ 区域在哮喘发病机制中的作用。HLA-DQA1 是继先前鉴定的 HLA-DRA、HLA-DQB1 和 HLA-DQA2 之后，第四个与哮喘相关的 HLA 家族成员。
