Dataset Information

DNA methylation is associated with lung function in never smokers.

ABSTRACT:

Background

Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked. Therefore, we aimed to identify differential DNA methylation associated with lung function in never smokers.

Methods

We determined epigenome-wide DNA methylation levels of 396,243 CpG-sites (Illumina 450?K) in blood of never smokers in four independent cohorts, LifeLines COPD&C (N =?903), LifeLines DEEP (N =?166), Rotterdam Study (RS)-III (N =?150) and RS-BIOS (N =?206). We meta-analyzed the cohort-specific methylation results to identify differentially methylated CpG-sites with FEV₁/FVC. Expression Quantitative Trait Methylation (eQTM) analysis was performed in the Biobank-based Integrative Omics Studies (BIOS).

Results

A total of 36 CpG-sites were associated with FEV₁/FVC in never smokers at p-valueConclusionsWith the identification of 35 CpG-sites that are unique for never smokers, our study shows that DNA methylation is also associated with FEV₁/FVC in subjects that never smoked and therefore not merely related to smoking.

SUBMITTER: de Vries M

PROVIDER: S-EPMC6889726 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

DNA methylation is associated with lung function in never smokers.

de Vries Maaike M Nedeljkovic Ivana I van der Plaat Diana A DA Zhernakova Alexandra A Lahousse Lies L Brusselle Guy G GG Amin Najaf N van Duijn Cornelia M CM Vonk Judith M JM Boezen H Marike HM

Respiratory research 20191202 1

<h4>Background</h4>Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked. Therefore, we aimed to identify differential DNA methylation associated with lung function in never smokers.<h4>Methods</h4>We determined epigenome-wide DNA methylation levels of 396,243 CpG-sites (Il ...[more]

PMID: 31791327

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Project description:BACKGROUND:Impaired lung health represents a significant burden on global health, including chronic obstructive pulmonary disease (COPD) and lung cancer. Given its global health impact, it is important to understand the determinants of impaired lung function and its relation to lung cancer risk independent of smoking. However, to date, no study has evaluated determinants of impaired lung function in a cohort exclusively of never-smokers, who also represent a growing proportion of all lung cancers. METHODS:A total of 222,274 never-smokers with reproducible spirograms were identified in the UK Biobank population-based cohort and included in the analysis. Baseline volumetric measures of lung function, including forced expiratory volume in 1-s (FEV1) and forced vital capacity (FVC), were used to define lung function impairment. Determinants of impaired lung function were evaluated using Poisson regression with robust variance estimation. The added value of lung function in lung cancer prediction was evaluated using Fine and Gray regression accounting for the competing risk of all-cause mortality. FINDINGS:Lung function impairment was associated with low birthweight, ambient air pollution (PM2·5 μg/mm3), and overweight, after adjustment for other important risk factors. We observed modest improvement in discrimination by adding lung function to our lung cancer prediction model for never-smokers. The highest optimism-corrected AUC at 3 (0·700, 95% CI: 0·654-0·734) and 5 years (0·694, 95% CI: 0·658-0·736) included FEV1 (% of GLI predicted FEV1), while the highest AUC at 7 years was based on the inclusion of FEV1/FVC (0·722, 95% CI: 0·687-0·762). INTERPRETATION:We identified several modifiable risk factors associated with increased risk of lung function impairment among lifetime never-smokers in UKB. We achieved moderate discrimination for lung cancer risk-prediction for never-smokers, and found modest improvement with the inclusion of lung function. FUND: This study was supported by a Canada Research Chair to RJH.

Dataset Information

DNA methylation is associated with lung function in never smokers.

Background

Methods

Results

Publications

DNA methylation is associated with lung function in never smokers.

Similar Datasets

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