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Background  Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable. We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.    Methods  Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), forced expiratory flow from the 25 th  to 75 th  percentile (FEF 25–75 ), the FEV 1 /FVC ratio, and the FEF 25–75 /FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.    Results  Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency ≥ 10%, genotype call rate ≥ 80%, and Hardy-Weinberg equilibrium p-value ≥ 0.001. A SNP in the interleukin 6 receptor ( IL6R ) on chromosome 1 was among the best results for percent predicted FEF 25–75 . A non-synonymous coding SNP in glutathione S-transferase omega 2 ( GSTO2 ) on chromosome 10 had top-ranked results studying the mean FEV 1  and FVC measurements from two examinations. SNPs nearby the  SOD3  and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.    Conclusion   GSTO2  and  IL6R  are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at   .

Framingham Heart Study genome-wide association: results for pulmonary function measures