Genome-Wide Association Study Identifies <em>HLA-DP</em> as a Susceptibility Gene for Pediatric Asthma in Asian Populations

Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10−8) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (Pcombined = 2.3×10−10, odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5×10−10, OR = 1.52, and DPB1*0901: P = 2.0×10−7, OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.哮喘是一种受遗传与环境因素共同影响的复杂表型。我们针对938名日本儿童哮喘患者与2376名对照个体开展了全基因组关联研究（Genome-Wide Association Study, GWAS）。在该GWAS中呈现强关联（P<1×10^-8）的单核苷酸多态性（Single-Nucleotide Polymorphism, SNPs），我们在独立日本队列（818名病例、1032名对照）以及韩国队列（835名病例、421名对照）中进行了进一步基因分型。位于HLA-DPA1与HLA-DPB1基因之间的SNP rs987870，在3个独立人群中均与儿童哮喘呈显著关联（合并P值=2.3×10^-10，比值比[odds ratio, OR]=1.40）。HLA-DP等位基因分析显示，处于强连锁不平衡状态的DPA1*0201与DPB1*0901，均与儿童哮喘呈强关联（DPA1*0201：P=5.5×10^-10，OR=1.52；DPB1*0901：P=2.0×10^-7，OR=1.49）。本研究结果表明，HLA-DP基因座的遗传变异与亚洲人群儿童哮喘的发病风险显著相关。