Laboratory for Respiratory Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa, Japan.
Nat Genet. 2011 Jul 31;43(9):893-6. doi: 10.1038/ng.887.
Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors. Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 × 10(-12)), a locus on chromosome 10p14 (P = 1.79 × 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 × 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.
支气管哮喘是一种常见的炎症性疾病，由遗传和环境因素相互作用引起。通过对日本人群中总计 7171 例成年哮喘（病例）和 27912 例对照的全基因组关联研究和复制研究，我们鉴定出与成年哮喘易感性相关的五个位点。除了先前报道的主要组织相容性复合体和 TSLP-WDR36 位点外，我们还鉴定出三个额外的位点：位于染色体 4q31 上的 USP38-GAB1 位点（合并 P = 1.87×10(-12)）、位于染色体 10p14 上的位点（P = 1.79×10(-15)）和位于染色体 12q13 上的基因丰富区域（P = 2.33×10(-13)）。我们在主要组织相容性复合体区域中观察到与成年哮喘最显著相关的 rs404860 （P = 4.07×10(-23)），这与 rs2070600 非常接近，后者是先前在全基因组关联研究中与肺功能 FEV(1)/FVC 相关的 SNP。我们的研究结果为哮喘易感性的遗传贡献提供了更好的理解。
