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Chronic obstructive...
Chronic obstructive pulmonary disease is associated with epigenome-wide differential methylation in BAL lung cells
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- Eriksson Ström, Jonas (författare)
- Umeå universitet,Avdelningen för medicin
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- Kebede Merid, Simon (författare)
- Department of Clinical Sciences and Education, Karolinska Institute, Stockholm, Sweden
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- Pourazar, Jamshid, 1953- (författare)
- Umeå universitet,Avdelningen för medicin
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- Blomberg, Anders, 1961- (författare)
- Umeå universitet,Avdelningen för medicin
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- Lindberg, Anne (författare)
- Umeå universitet,Avdelningen för medicin
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- Ringh, Mikael V. (författare)
- Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Center for Molecular Medicine, 5Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
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- Hagemann-Jensen, Michael (författare)
- Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
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- Ekström, Tomas J. (författare)
- Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
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- Behndig, Annelie F., 1963- (författare)
- Umeå universitet,Avdelningen för medicin
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- Melén, Erik (författare)
- Department of Clinical Sciences and Education, Karolinska Institute, Stockholm, Sweden; Sachs Children’s Hospital, Stockholm, Sweden
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(creator_code:org_t)
- American Thoracic Society, 2022
- 2022
- Engelska.
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - : American Thoracic Society. - 1044-1549 .- 1535-4989. ; 66:6, s. 638-647
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on BAL cells. Bronchoscopies were performed in 18 subjects with COPD and 15 control subjects (ex- and current smokers). DNA methylation was measured using the Illumina MethylationEPIC BeadChip Kit, covering more than 850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, 2) accelerated aging using Horvath's epigenetic clock, 3) correlation with gene expression, and 4) colocalization with genetic variation. We found 1,155 Bonferroni-significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were colocalized with COPD-associated SNPs. To the best of our knowledge, this is the first epigenome-wide association study of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly affect expression. Almost half of DMPs were colocated with SNPs identified in previous genome-wide association studies of COPD, suggesting joint genetic and epigenetic pathways related to disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- chronic obstructive pulmonary disease
- DNA methylation
- epigenetics
- BAL cells
- gene expression
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- art (ämneskategori)
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Eriksson Ström, ...
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Kebede Merid, Si ...
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Pourazar, Jamshi ...
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Blomberg, Anders ...
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Lindberg, Anne
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Ringh, Mikael V.
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Hagemann-Jensen, ...
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Ekström, Tomas J ...
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Behndig, Annelie ...
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Melén, Erik
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