|Session Title: Statistical Genetics and Genetic Epidemiology Session Type: Poster|
|Session Location: Exhibit Hall, Level 2, Convention Center Session Time: Wed 10:00AM-7:00PM|
|Program Number: 654W Presentation Time: Wed, Oct 12, 2011, 3:00PM-4:00PM|
|Keywords: Statistical Genetics and Genetic Epidemiology, KW015 - CANDIDATE GENE, KW073 - GENETIC EPIDEMIOLOGY, KW086 - IDENTIFICATION OF DISEASE GENES, KW153 - RESPIRATORY SYSTEM|
Testing GWAS SNPs for COPD and lung function in a Polish cohort with severe COPD. M. Hardin1, J. Zielinski2, E. Wan3, C. P. Hersh3, P. J. Castaldi3, E. Schwinder3, P. Sliwinski2, I. Hawrylkiewicz2, M. Cho3, E. K. Silverman3 1) Pulmonary Critical Care, Channing Laboratory, Brigham and Women's Hospital, Boston, MA; 2) National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland; 3) The Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.|
Rationale: Previous genome-wide association studies (GWAS) have demonstrated genetic loci associated with COPD. More recently, in the CHARGE and SpiroMeta consortiums, additional loci associated with lung function (FEV1 and FEV1/FVC) have been identified. In order to confirm previously identified COPD loci and to assess pulmonary function loci as COPD genetic determinants, we performed candidate gene analyses of loci previously associated with COPD and lung function in a novel cohort with severe to very severe COPD. Methods: All subjects were Caucasian smokers from Poland. 315 COPD cases and 338 controls were enrolled. All subjects completed a respiratory questionnaire, performed standardized spirometry, and provided blood samples for testing. From previous GWAS studies, we included four single nucleotide polymorphisms (SNPs) that had been associated with COPD: FAM13A(rs7671167), HHIP(rs13118928), IREB2(rs13180), and CHRNA3/5(rs8034191), as well as four SNPs that have been associated with lung function in general population samples: AGER(rs2070600), ADCY2(rs11134242), THSD4(rs4316710), and INTS12(rs17096090). We tested for association with COPD using logistic regression, controlling for age, gender and pack-years. Results: Subjects with COPD were older (62 vs 58 years, p<0.01) with greater pack-years (45 vs 34 pack-years, p<0.01). There were more males than females but gender was equally distributed among cases and controls. Cases had significantly worse lung function (FEV1 31% predicted vs 103% predicted, p<0.01; FEV1/FVC 36% vs 76%, p<0.01). Among SNPs previously associated with COPD, CHRNA3/5 (OR 1.8 [1.4,2.4], p = 1x10-8), IREB2 (OR 0.7[0.5, 0.9], p = 0.003), and HHIP (OR 0.7 [0.5,0.9], p= 0.001) demonstrated significant association with COPD. FAM13A (OR 0.8 [0.7,1.1], p=0.06) approached statistical significance. The CHRNA3/5 locus was no longer significant when adjusting for the presence of the IREB2 locus. Among the SNPs associated with lung function, ADCY2 demonstrated a significant association with severe COPD (OR 1.3 [1.1,1.7], p=0.007); however, SNPs near AGER (p=0.25), THSD4 (p=0.18) and INTS12 (p=0.3) did not demonstrate association. Conclusion: In a population of Polish subjects with severe to very severe COPD, we demonstrate replication of association between three SNPs and COPD (CHRNA3/5, IREB2 and HHIP) as well as association with COPD of two loci that have been associated with lung function (HHIP and ADCY2).
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