Abstract
Previous genome-wide association studies (GWAS) have identified novel genetic factors associated with cross-sectional lung Rationale: function reflecting lung function growth as well as decline. Accelerated lung function decline is associated with increased risk of mortality. We have conducted the first GWAS on age-related lung function decline stratifying all analyses by asthma status a priori. We tested 2.5 million single nucleotide polymorphisms (SNPs) for associations with annual decline in FEV1 (forced expiratory Methods: volume in 1 second), FVC (forced vital capacity) and FEV1/FVC in three cohort studies of European ancestry (N=4’118, Epidemiological study on the Genetics and Environment of Asthma (EGEA), Swiss study on Air Pollution And Lung Disease In Adults (SAPALDIA) and European Community Respiratory Health Survey (ECRHS)). Standardized residuals, obtained from study-specific linear regressions of annual decline in FEV1, FEV1/FVC and FVC on age, height and centre in sexand asthma status-specific strata, were used for genome-wide testing adjusted for ancestry-informative principal components. The study-specific regression coefficients for additive genetic effects were combined across cohorts in inverse-variance weighted fixed and random effects meta-analyses. Heterogeneity of genetic estimates
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