DNA Methylation Is Predictive of Mortality in Current and Former Smokers

Smoking results in at least a decade lower life expectancy. Mortality among current smokers is two to three times as high as never smokers. DNA methylation is an epigenetic modification of the human genome that has been associated with both cigarette smoking and mortality. We sought to identify DNA...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2020-05, Vol.201 (9), p.1099-1109
Main Authors: Morrow, Jarrett D, Make, Barry, Regan, Elizabeth, Han, MeiLan, Hersh, Craig P, Tal-Singer, Ruth, Quackenbush, John, Choi, Augustine M K, Silverman, Edwin K, DeMeo, Dawn L
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - blood
Chronic obstructive pulmonary disease
Cohort Studies
DNA Methylation
Epidemiology
Epigenesis, Genetic
Female
Genetics
Humans
Male
Medical prognosis
Middle Aged
Mortality
Original
Predictive Value of Tests
Pulmonary Disease, Chronic Obstructive - genetics
Pulmonary Disease, Chronic Obstructive - mortality
Smoking
Smoking - genetics
Smoking - mortality
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Summary:Smoking results in at least a decade lower life expectancy. Mortality among current smokers is two to three times as high as never smokers. DNA methylation is an epigenetic modification of the human genome that has been associated with both cigarette smoking and mortality. We sought to identify DNA methylation marks in blood that are predictive of mortality in a subset of the COPDGene (Genetic Epidemiology of COPD) study, representing 101 deaths among 667 current and former smokers. We assayed genome-wide DNA methylation in non-Hispanic white smokers with and without chronic obstructive pulmonary disease (COPD) using blood samples from the COPDGene enrollment visit. We tested whether DNA methylation was associated with mortality in models adjusted for COPD status, age, sex, current smoking status, and pack-years of cigarette smoking. Replication was performed in a subset of 231 individuals from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study. We identified seven CpG sites associated with mortality (false discovery rate 
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201902-0439OC