Abstract
DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV 1 , FEF 25–75% ) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1039-1055 |
| Number of pages | 17 |
| Journal | Epigenetics |
| Volume | 13 |
| Issue number | 10-11 |
| DOIs | |
| State | Published - Nov 2 2018 |
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Keywords
- Biomarker
- DNA methylation
- lung function decline
- pulmonary function
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
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Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans : an epigenome-wide study in the NAS and KORA cohorts. / Carmona, Juan Jose; Barfield, Richard T.; Panni, Tommaso; Nwanaji-Enwerem, Jamaji C.; Just, Allan C.; Hutchinson, John N.; Colicino, Elena; Karrasch, Stefan; Wahl, Simone; Kunze, Sonja; Jafari, Nadereh; Zheng, Yinan; Hou, Lifang; DeMeo, Dawn L.; Litonjua, Augusto A.; Vokonas, Pantel S.; Peters, Annette; Lin, Xihong; Schwartz, Joel; Schulz, Holger; Baccarelli, Andrea A.
In: Epigenetics, Vol. 13, No. 10-11, 02.11.2018, p. 1039-1055.Research output: Contribution to journal › Article
TY - JOUR
T1 - Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans
T2 - an epigenome-wide study in the NAS and KORA cohorts
AU - Carmona, Juan Jose
AU - Barfield, Richard T.
AU - Panni, Tommaso
AU - Nwanaji-Enwerem, Jamaji C.
AU - Just, Allan C.
AU - Hutchinson, John N.
AU - Colicino, Elena
AU - Karrasch, Stefan
AU - Wahl, Simone
AU - Kunze, Sonja
AU - Jafari, Nadereh
AU - Zheng, Yinan
AU - Hou, Lifang
AU - DeMeo, Dawn L.
AU - Litonjua, Augusto A.
AU - Vokonas, Pantel S.
AU - Peters, Annette
AU - Lin, Xihong
AU - Schwartz, Joel
AU - Schulz, Holger
AU - Baccarelli, Andrea A.
PY - 2018/11/2
Y1 - 2018/11/2
N2 - DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV 1 , FEF 25–75% ) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.
AB - DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis. Using linear mixed models, we performed an Epigenome Wide Association Study (EWAS) between DNA methylation at CpG dinucleotides and longitudinal lung function (FVC, FEV 1 , FEF 25–75% ) decline and aging with initial discovery in the Normative Aging Study, and replication in the Cooperative Health Research in the Region of Augsburg cohort. We identified two metastable epigenetic loci associated with either poor lung function and aging, cg05575921 (AHRR gene), or lung function independently of aging, cg06126421 (IER3 gene). These loci may inform basic mechanisms associated with pulmonary function, pathogenesis, and aging. Human epigenomic variation, may help explain features of lung function decline and related pathophysiology not attributable to DNA sequence alone, such as accelerated pulmonary decline in smokers, former smokers, and perhaps non-smokers. Our EWAS across two cohorts, therefore, will likely have implications for the human population, not just the elderly.
KW - Biomarker
KW - DNA methylation
KW - lung function decline
KW - pulmonary function
UR - http://www.scopus.com/inward/record.url?scp=85055351741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055351741&partnerID=8YFLogxK
U2 - 10.1080/15592294.2018.1529849
DO - 10.1080/15592294.2018.1529849
M3 - Article
C2 - 30343628
AN - SCOPUS:85055351741
VL - 13
SP - 1039
EP - 1055
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 10-11
ER -