Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts

Juan Jose Carmona, Richard T. Barfield*, Tommaso Panni, Jamaji C. Nwanaji-Enwerem, Allan C. Just, John N. Hutchinson, Elena Colicino, Stefan Karrasch, Simone Wahl, Sonja Kunze, Nadereh Jafari, Yinan Zheng, Lifang Hou, Dawn L. DeMeo, Augusto A. Litonjua, Pantel S. Vokonas, Annette Peters, Xihong Lin, Joel Schwartz, Holger SchulzAndrea A. Baccarelli

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1039-1055
Number of pages17
JournalEpigenetics
Volume13
Issue number10-11
DOIs
StatePublished - Nov 2 2018

Fingerprint

DNA Methylation
Lung
Epigenomics
Biomarkers
Vulnerable Populations
Regulator Genes
Genes
Linear Models
Cohort Studies
Health
Research

Keywords

  • Biomarker
  • DNA methylation
  • lung function decline
  • pulmonary function

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Carmona, J. J., Barfield, R. T., Panni, T., Nwanaji-Enwerem, J. C., Just, A. C., Hutchinson, J. N., ... Baccarelli, A. A. (2018). Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts. Epigenetics, 13(10-11), 1039-1055. https://doi.org/10.1080/15592294.2018.1529849
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. / Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans : an epigenome-wide study in the NAS and KORA cohorts. In: Epigenetics. 2018 ; Vol. 13, No. 10-11. pp. 1039-1055.
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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.",
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Carmona, JJ, Barfield, RT, Panni, T, Nwanaji-Enwerem, JC, Just, AC, Hutchinson, JN, Colicino, E, Karrasch, S, Wahl, S, Kunze, S, Jafari, N, Zheng, Y, Hou, L, DeMeo, DL, Litonjua, AA, Vokonas, PS, Peters, A, Lin, X, Schwartz, J, Schulz, H & Baccarelli, AA 2018, 'Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts', Epigenetics, vol. 13, no. 10-11, pp. 1039-1055. https://doi.org/10.1080/15592294.2018.1529849

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 journalArticle

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.

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KW - Biomarker

KW - DNA methylation

KW - lung function decline

KW - pulmonary function

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