Table 4 Overview of studies reporting results of differential DNA methylation with lung function or COPD in whole blood
From: DNA methylation is associated with lung function in never smokers
Study | Study population | Trait | Adjustment included in model | DNA methylation platform | Number of CpG-sites available for comparison |
|---|---|---|---|---|---|
Epigenome-wide association study of lung function level and its change Imboden et al., 2019 [17] | Discovery-replication approach. Discovery included 3 cohorts (N=2043) and replication included 7 cohorts (Adult: N=3327, Childhood: N=420) - Smoking status: self-reported, subjects with and without smoking history; never smokers only | - FEV1 - FVC - FEV1/FVC Analyses were performed twice: with and without adjustment for smoking status and pack years | - Age - Age2 - Height - Height2 deviation - Sex - Sex Age, Age2, height, Height2 deviation - Education - BMI - Spirometer type - Study Center - Blood cell composition | Discovery: Illumina Infinium Human Methylation 450 K BeadChip and EPIC BeadChip Replication: various arrays for the discovery-identified CpG-sites only | Without smoking adjustment: 56a With smoking adjustment: 12a Never smokers: 8 (from discovery). None of the CpG sites were replicateda |
No association between DNA methylation and COPD in never and current smokers De Vries et al., 2018 [16] | Non-random selection from LifeLines cohort (N=1561 subjects) - Smoking status: Stratified for smoking (658 smokers and 903 never smokers) | - COPD (defined as FEV1/FVC ≤ 0.7) | - Sex - Age - Pack years (in smoking stratified analysis) - Batch effects - Blood cell composition | Illumina Infinium Human Methylation450K BeadChip array - Number of included probes: 420,938 | Smokers: 19492b Never smokers: 19393b |
Lung function discordance in monozygotic twins and ssociated differences in blood DNA methylation Bolund et al., 2017 [11] | Sub-population of twins from the Middle-Aged Danish Twin (MADT) study (N=169 twin pairs) - Smoking status: subjects with and without smoking history | Intra-pair difference in z-score calculated as “superior” minus “inferior” twin at baseline and during follow-up period for: - FEV1 - FVC - FEV1/FVC | - Sex - Age - BMI - Pack years - Smoking status at follow-up - Blood cell composition Intra-pair difference was calculated for all the variables | Illumina Infinium Human Methylation450K BeadChip array - Number of included probes: 453,014 | 37a |
Epigenome-wide association study of chronic obstructive pulmonary disease and lung function in Koreans Lee et al., 2017 [12] | Sample of Korean COPD cohort (N=100 subjects) - Smoking status: subjects with and without smoking history | - COPD status (defined as FEV1/FVC < 0.7) - FEV1 - FVC - FEV1/FVC | - Sex - Age - Height - Smoking status - Pack years - Blood cell composition | Illumina Infinium Human Methylation450K BeadChip array - Number of included probes: 402,508 | 16a |
Differential DNA methylation marks and gene comethylation of COPD in African-Americans with COPD exacerbations Busch et al., 2016 [13] | Sample of PA-SCOPE AA study population (N=362 subjects) - Smoking status: smokers > 20 pack years | - COPD (defined as FEV1/FVC ≤ 0.7 and FEV1 ≤ 80%) | - Sex - Age - Pack years - Batch number - Blood cell composition | Illumina Infinium Human Methylation27K BeadChip array - Number of included probes: 19,302 | 12a |
The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort Marioni et al., 2015 [15] | The Lothian Birth Cohort of 1936 (N=1091) - Smoking status: self-reported, subjects with and without smoking history | - FEV1 | - Sex - Age - Height - Smoking status - Blood cell composition | Illumina Infinium Human Methylation450K BeadChip array - Number of included probes: 450,726 | 2a |
Variable DNA methylation is associated with chronic obstructive pulmonary disease and lung function Qiu et al., 2012 [10] | Test-replication approach in 2 family-based cohorts (N=1085 and 369 subjects) - Smoking status: subjects with and without smoking history | - COPD status (FEV1/FVC ≤0.7 and FEV1 ≤70%) - FEV1/FVC - FEV1 | - Random family effect | Illumina Infinium Human Methylation27K BeadChip array - Number of included probes: 26,485 | 349a |
Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population Bell et al., 2012 [14] | Sample of the TwinsUK cohort (N=172 female twin pairs) - Smoking status: unknown | - FEV1 - FVC | - Age - Batch effects | Illumina Infinium Human Methylation27K BeadChip array - Number of included probes: 24,641 | 1a |