Rationale: Lung function measures are heritable traits that predict population morbidity and mortality and are essential for
the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect
these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of
Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general
population (the SpiroMeta consortium). Objectives: To comprehensively analyse previously reported genetic associations with lung function measures, and to
investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in
a large population sample.
Methods: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/210 kb), after conducting a
systematic review of the literature in the PubMed database for genetic association studies reporting lung function
associations.
Results: The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1
or FEV1/FVC traits using a carefully defined significance threshold of 1.361025
. The most significant loci associated with
FEV1 include SNPs tagging MACROD2 (P = 6.8161025
), CNTN5 (P = 4.3761024
), and TRPV4 (P = 1.5861023
). Among eversmokers,
SERPINA1 showed the most significant association with FEV1 (P = 8.4161025
), followed by PDE4D (P = 1.2261024
).
The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.3861024
), and ESR1 (P = 5.4261024
) among
ever-smokers.
Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for
association with lung function measures in the SpiroMet