A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13
A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13
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DOI：
10.1093/hmg/ddr524
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发表时间：
2012-02-15
影响因子：
3.5
通讯作者：
Silverman, Edwin K.
中科院分区：
文献类型：
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作者：
Cho, Michael H.;Castaldi, Peter J.;Silverman, Edwin K.
慢性阻塞性肺疾病（COPD）的遗传风险因素在很大程度上仍然未知。迄今为止，规模有限的全基因组关联研究（GWAS）已在CHRNA 3/CHRNA 5/IREB 2、HHIP和FAM 13 A确定了几个新的COPD风险位点;其他位点可能通过更大规模的研究确定。我们使用来自四个队列的总共3499例病例和1922例对照受试者进行了GWAS：COPD纵向评估以确定预测性替代终点（ECLIPSE）;规范性衰老研究（NAS）和国家肺气肿治疗试验（NETT）;挪威卑尔根（卑尔根）;以及COPDGene研究。在Illumina平台上进行基因分型，使用1000个基因组数据插补其他标志物;使用固定效应荟萃分析总结结果。我们在染色体19 q13上发现了一个新的全基因组显著位点（rs7937，OR = 0.74，P = 2.9 × 10（-9））。基因分型这个单核苷酸多态性（SNP）和另一个连锁不平衡附近的SNP在来自基于家族的国际COPD遗传学网络研究（ICGN）的2859例受试者中，rs 2604894显示了COPD相关性的支持性证据（rs7937和rs 2604894的P = 0.28和0.11）、使用支气管扩张剂前FEV 1（P = 0.08和0.04）和重度（GOLD 3和4）COPD（P = 0.09和0.017）。该区域包括RAB 4 B、EGLN 2、MIA和CYP 2A 6，并且先前已被鉴定与吸烟行为相关。
The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genomewide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 x 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV1 (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.