25 research outputs found
Italian top 12 genotyped SNP list (2-tailed logistic regression, n = 759 overall, n = 593 exposed only).
<p>Italian top 12 genotyped SNP list (2-tailed logistic regression, n = 759 overall, n = 593 exposed only).</p
Manhattan plot of genotyped SNPs from logistic additive model.
<p>A) all samples, B) exposed samples.</p
Summary statistics of all the subjects included in the Italian GWAS.
<p>Summary statistics of all the subjects included in the Italian GWAS.</p
Regional replication of Italian top signals in the Australian study for 5 out of the 20 regions.
<p>(1-tailed binomial test and meta-analysis).</p>a<p>NCBI36/hg18.</p>b<p>Italian study.</p>c<p>Australian study.</p
Nested multivariate logistic regression models: 1) model 1, without genetic component; 2) model 2, with genetic component.
*<p>adjusted for age, gender and center of recruitment.</p><p>MODEL 1: AIC = 871.3, AUC = 0.76.</p><p>MODEL 2: AIC = 730.27, AUC = 0.86.</p
Receiver Operating Curves (ROC) for the two multivariate models including asbestos exposure 1) without and 2) with the 10 most robust and significant genetic variants.
<p>Receiver Operating Curves (ROC) for the two multivariate models including asbestos exposure 1) without and 2) with the 10 most robust and significant genetic variants.</p
eQTL: <i>PVT1</i> and <i>MYC</i> gene-expression levels in blood cells across rs78941347 genotypes.
<p>eQTL: <i>PVT1</i> and <i>MYC</i> gene-expression levels in blood cells across rs78941347 genotypes.</p
Region-, Gene- and GO process-based analysis on top SNPs (1-tailed binomial test, n = 759, alpha 0.0025, alpha = 0.01, alpha = 0.025, respectively).
<p>Region-, Gene- and GO process-based analysis on top SNPs (1-tailed binomial test, n = 759, alpha 0.0025, alpha = 0.01, alpha = 0.025, respectively).</p
A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample.
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 (+/−10 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 1.3×10−5. The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81×10−5), CNTN5 (P = 4.37×10−4), and TRPV4 (P = 1.58×10−3). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38×10−4), and ESR1 (P = 5.42×10−4) among ever-smokers.
Conclusions: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population
Study design. Each step includes non-overlapping, independent datasets.
<p>Study design. Each step includes non-overlapping, independent datasets.</p