Lung function decline in COPACETIC according to rs1051730 and rs8034191 genotypes.

#<p>significant compared to the GG genotype for rs1051730 (p = 0.026).</p>*<p>significant compared to AA genotype for rs8034191 (p = 0.009 and p = 0.017, respectively for FEV₁/FVC and MEF₅₀ decline).</p

Baseline characteristics for the COPACETIC cohort according to rs1051730 and rs8034191 genotypes.

<p>FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; MEF₅₀ maximum expiratory flow when 50% of the FVC has been exhaled; GOLD: global initiative for chronic obstructive lung disease. Percentages are column percentages. Genotyping succeeded in 1226 (100%) and 1224 (99.8%) COPACETIC participants, respectively for rs1051730 and rs8034191.</p

Baseline Characteristics for LEUVEN participants stratified for the clinical impact of airflow obstruction.

<p>Abbreviations are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053219#pone-0053219-t001" target="_blank">Table 1</a>. Percentages are column percentages. The 366 asymptomatic smokers are population-based participants of the Dutch-Belgian lung cancer screening trial (NELSON). None of them were previously diagnosed with COPD. However, 148 subjects (40.4%) were found to have an obstructive lung function (based on FEV₁/FVC<0.70) at inclusion. Eleven subjects (2%), that were followed-up at the outpatient clinic because of symptoms compatible with COPD, did not fulfill the criterion of COPD (FEV₁/FVC>0.70). Five patients with end-stage COPD were not actively listed for lung transplantation because of their current smoking status at inclusion.</p

Baseline characteristics for the LEUVEN group according to rs1051730 and rs8034191 genotypes.

<p>Genotyping succeeded in 874 (99%) and 883 (100%) LEUVEN participants, respectively for rs1051730 and rs8034191.</p

Characteristics for COPACATIC and LEUVEN at baseline and after three-year follow-up for COPACETIC.

<p>FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; COPD: chronic obstructive pulmonary disease; GOLD: global initiative for chronic obstructive lung disease; N/A: non-applicable. Percentages are column percentages. Of the LEUVEN participants, 653 subjects were diagnosed with COPD (FEV₁/FVC<0.70).</p

Linkage Disequilibrium Map for the COPD-associated variants in the 15q24/25 region.

<p>Red corresponds to r2≥0.8. Values for D′ are included in the text of boxes. The genomic positions were retrieved from the NCBI dbSNP identifier (NCBI Human genome Build 36 location). The CHRNA 5 gene variant, rs55853698, is not present in the HapMap <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053219#pone.0053219-Altshuler1" target="_blank">[21]</a>.</p

Overview of populations.

<p>Populations and corresponding period of data collection, type of population, genotyping platform and soft-ware used for imputation.</p><p>NA = not applicable.</p

Meta-analysis of the effect of rs6577641 on mRNA expression levels of <i>SATB1</i> in the lung^*.

<p>*To assess the effect of the SNP rs6577641 on gene expression, a Kruskal-Wallis test was performed. This test generates a p-value, but does not give a direction of the effect. To assess the direction of the effect, a Spearman's correlation test was performed. Next, a Z-score was calculated for each center and a meta-analysis performed for each of the three <i>SATB1</i> probes across all centers. Finally, a meta-analysis for all three <i>SATB1</i> probes was performed across all centers. This generated a Z-score of −5.87 and a corresponding p-value of 4.3*10⁻⁹, indicating that the susceptibility G allele of the SNP rs6577641 increases <i>SATB1</i> expression.</p

<i>SATB1</i>, <i>MUC5AC</i> and <i>FOXJ1</i> mRNA expression levels during mucociliary human airway epithelial cell differentiation (n = 2 donors).

<p>Expression of <i>SATB1</i>, the identified gene in our study, <i>MUC5AC</i> a marker of mucus, and <i>FOXJ1</i>, representing ciliated cells in epithelial cell culture on air liquid interface.</p

Meta-analysis of top SNPs associated with CMH in replication cohorts, in identification and replication cohorts and corresponding direction of effect in all cohorts and associated feature and gene(s).

<p>MAF = minor allele frequency in NELSON;</p><p>*Direction of effect per cohort: each sign reflects one cohort, direction of effect is presented by: + = (OR>1.05), − = (OR<0.95), 0 = (0.95Table 2; OR is odds ratio; Q is p-value for heterogeneity;</p>#<p>means corresponding SNP is located in an intron in this gene.</p