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Published on: December 10, 2012
Epigenome-wide association study of lung function level and its change
Medea Imboden1,2,3, Matthias Wielscher4,5,3, Faisal I Rezwan6,3
1Chronic Disease Epidemiology Unit, Dept of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.
DNA methylation (DNAme) in adults is strongly linked to smoking and lung function. These DNAme markers may help identify individuals with poor lung function or accelerated decline.
Area of Science:
- Epigenetics
- Pulmonology
- Environmental Health
Background:
- Differential DNA methylation (DNAme) is linked to environmental exposures affecting lung function.
- Direct evidence on DNAme related to lung function is limited.
- Epigenome-wide association studies (EWAS) can identify DNAme markers associated with lung function.
Purpose of the Study:
- To conduct an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.
- To identify and validate DNAme markers associated with lung function levels and changes over time.
- To explore the relationship between smoking and lung function-associated DNAme.
Main Methods:
- A discovery-replication EWAS design using longitudinal data from three adult cohorts (n=2043).
- DNA methylation (DNAme) and spirometry (FEV1, FVC) measured twice, 6-15 years apart.
- Meta-analysis of discovery and replication cohorts (adults: n=3327; children: n=420), including never-smokers.
Main Results:
- EWAS signals were enriched for smoking-related DNAme.
- 57 lung function DNAme markers were replicated in adults, all previously linked to smoking.
- cg05575921 (AHRR) showed the strongest association with lung function (FEV1/FVC). A 10-marker score associated with smoking also correlated with lung function.
Conclusions:
- Lung function-associated DNAme signals in adults are predominantly smoking-related.
- These DNAme markers may have clinical utility in identifying poor lung function and accelerated decline.
- Further research with larger cohorts and more time points is needed to identify DNAme in never-smokers and children.
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