A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13

作者：Cho Michael H^*; Castaldi Peter J; Wan Emily S; Siedlinski Mateusz; Hersh Craig P; Demeo Dawn L; Himes Blanca E; Sylvia Jody S; Klanderman Barbara J; Ziniti John P; Lange Christoph; Litonjua Augusto A; Sparrow David; Regan Elizabeth A; Make Barry J; Hokanson John E; Murray Tanda; Hetmanski Jacqueline B; Pillai Sreekumar G; Kong Xiangyang; Anderson Wayne H; Tal Singer Ruth; Lomas David A; Coxson Harvey O; Edwards Lisa D; MacNee William; Vestbo Jorgen

来源：Human Molecular Genetics, 2012, 21(4): 947-957.

DOI：10.1093/hmg/ddr524

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%264) 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.

• 出版日期2012-2-15
• 单位河北医科大学