A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
复制标题
DOI：
10.1038/ng.2830
复制
发表时间：
2014-01-01
期刊：
影响因子：
30.8
通讯作者：
Bisgaard, Hans
中科院分区：
文献类型：
--
作者：
Bonnelykke, Klaus;Sleiman, Patrick;Bisgaard, Hans
哮喘加重是儿童时期住院的最常见原因之一，但其潜在机制尚不清楚。我们对一种特殊的哮喘表型进行了全基因组关联研究，该表型的特征是在2至6岁之间反复出现严重的恶化，总共有1173例患者和2522名对照。病例从国家住院健康登记处确认，DNA从丹麦新生儿筛查生物库获得。我们确定了五个与全基因组显著相关的基因座。其中四个，GSDMB，IL33，Rad50和IL1RL1，以前被报道为哮喘易感基因，但在我们的队列中，这些基因的效应大小比以前的全基因组哮喘相关研究要大得多。我们还获得了一个新的易感基因CDHR3(编码钙粘素相关家族成员3)的有力证据，该基因在呼吸道上皮细胞中高表达。这些结果证明了在寻找哮喘易感基因中应用特定表型的力量。
Asthma exacerbations are among the most frequent causes of hospitalization during childhood, but the underlying mechanisms are poorly understood. We performed a genome-wide association study of a specific asthma phenotype characterized by recurrent, severe exacerbations occurring between 2 and 6 years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL1RL1, were previously reported as asthma susceptibility loci, but the effect sizes for these loci in our cohort were considerably larger than in the previous genome-wide association studies of asthma. We also obtained strong evidence for a new susceptibility gene, CDHR3 (encoding cadherin-related family member 3), which is highly expressed in airway epithelium. These results demonstrate the strength of applying specific phenotyping in the search for asthma susceptibility genes.