Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells
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...
Gespeichert in:
| Veröffentlicht in: | American journal of respiratory cell and molecular biology 2022-06, Vol.66 (6), p.638-647 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 647 |
|---|---|
| container_issue | 6 |
| container_start_page | 638 |
| container_title | American journal of respiratory cell and molecular biology |
| container_volume | 66 |
| creator | Eriksson Ström, Jonas Kebede Merid, Simon Pourazar, Jamshid Blomberg, Anders Lindberg, Anne Ringh, Mikael V Hagemann-Jensen, Michael Ekström, Tomas J Behndig, Annelie F Melén, Erik |
| description | 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
) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology,
) accelerated aging using Horvath's epigenetic clock,
) correlation with gene expression, and
) colocalization with genetic variation. We found 1,155 Bonferroni-significant (
|
| doi_str_mv | 10.1165/rcmb.2021-0403OC |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_454816</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2639227052</sourcerecordid><originalsourceid>FETCH-LOGICAL-c500t-ef73138ce1150011c263abe1faab5a5fe39bea1e81a718dcec69a54479770cee3</originalsourceid><addsrcrecordid>eNp9kstv1DAQxiMEoqVw54QsceGS4vEjcS5IS1qg0qLlwONoOd7JrktiL3bSqv89Xu1SUQ6cPLZ_881DX1G8BHoOUMm30Y7dOaMMSiooX7WPilOQXJaiUc3jHFMhSpCiOSmepXRNKTAF8LQ44ZKpSoE6LWK7jcE7S1ZdmuJsJ3eD5Ms8jMGbeEcuXEKTkFwlskgpWGcmXJNbN23J5c5t0IcRyx9ujZnse4zoJ2cG8hmn7d1gJhc8cZ68XyzJcvYb0uIwpOfFk94MCV8cz7Pi24fLr-2ncrn6eNUulqWVlE4l9jUHriwC5DuAZRU3HUJvTCeN7JE3HRpABaYGtbZoq8ZIIeqmrqlF5GdFedBNt7ibO72Lbswz6WCcPj79zBFqIYWC6r_8hfu-0CFu9DzOmlFolMj8uwOf4RFzA36KZniQ9vDHu63ehBvd5GKVkFngzVEghl8zpkmPLtm8IuMxzEnngRvGaipZRl__g16HOfq8vkzVjCtWS54peqBsDClF7O-bAar3htF7w-i9YfTBMDnl1d9D3Cf8cQj_DeA2v4Y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2672382753</pqid></control><display><type>article</type><title>Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>SWEPUB Freely available online</source><creator>Eriksson Ström, Jonas ; Kebede Merid, Simon ; Pourazar, Jamshid ; Blomberg, Anders ; Lindberg, Anne ; Ringh, Mikael V ; Hagemann-Jensen, Michael ; Ekström, Tomas J ; Behndig, Annelie F ; Melén, Erik</creator><creatorcontrib>Eriksson Ström, Jonas ; Kebede Merid, Simon ; Pourazar, Jamshid ; Blomberg, Anders ; Lindberg, Anne ; Ringh, Mikael V ; Hagemann-Jensen, Michael ; Ekström, Tomas J ; Behndig, Annelie F ; Melén, Erik</creatorcontrib><description>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
) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology,
) accelerated aging using Horvath's epigenetic clock,
) correlation with gene expression, and
) colocalization with genetic variation. We found 1,155 Bonferroni-significant (
< 6.74 × 10
) 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.</description><identifier>ISSN: 1044-1549</identifier><identifier>ISSN: 1535-4989</identifier><identifier>EISSN: 1535-4989</identifier><identifier>DOI: 10.1165/rcmb.2021-0403OC</identifier><identifier>PMID: 35286818</identifier><language>eng</language><publisher>United States: American Thoracic Society</publisher><subject>Aging ; BAL cells ; Chronic obstructive pulmonary disease ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; Epigenesis, Genetic ; Epigenetics ; Epigenome ; Gene expression ; Genetic diversity ; Genome-Wide Association Study ; Genomes ; Humans ; Lung ; Lung diseases ; Obstructive lung disease ; Original Research ; Pulmonary Disease, Chronic Obstructive - genetics</subject><ispartof>American journal of respiratory cell and molecular biology, 2022-06, Vol.66 (6), p.638-647</ispartof><rights>Copyright American Thoracic Society Jun 2022</rights><rights>Copyright © 2022 by the American Thoracic Society 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-ef73138ce1150011c263abe1faab5a5fe39bea1e81a718dcec69a54479770cee3</citedby><cites>FETCH-LOGICAL-c500t-ef73138ce1150011c263abe1faab5a5fe39bea1e81a718dcec69a54479770cee3</cites><orcidid>0000-0002-3434-988X ; 0000-0002-3292-7471</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35286818$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-201984$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:150185135$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Eriksson Ström, Jonas</creatorcontrib><creatorcontrib>Kebede Merid, Simon</creatorcontrib><creatorcontrib>Pourazar, Jamshid</creatorcontrib><creatorcontrib>Blomberg, Anders</creatorcontrib><creatorcontrib>Lindberg, Anne</creatorcontrib><creatorcontrib>Ringh, Mikael V</creatorcontrib><creatorcontrib>Hagemann-Jensen, Michael</creatorcontrib><creatorcontrib>Ekström, Tomas J</creatorcontrib><creatorcontrib>Behndig, Annelie F</creatorcontrib><creatorcontrib>Melén, Erik</creatorcontrib><title>Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells</title><title>American journal of respiratory cell and molecular biology</title><addtitle>Am J Respir Cell Mol Biol</addtitle><description>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
) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology,
) accelerated aging using Horvath's epigenetic clock,
) correlation with gene expression, and
) colocalization with genetic variation. We found 1,155 Bonferroni-significant (
< 6.74 × 10
) 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.</description><subject>Aging</subject><subject>BAL cells</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Epigenome</subject><subject>Gene expression</subject><subject>Genetic diversity</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humans</subject><subject>Lung</subject><subject>Lung diseases</subject><subject>Obstructive lung disease</subject><subject>Original Research</subject><subject>Pulmonary Disease, Chronic Obstructive - genetics</subject><issn>1044-1549</issn><issn>1535-4989</issn><issn>1535-4989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kstv1DAQxiMEoqVw54QsceGS4vEjcS5IS1qg0qLlwONoOd7JrktiL3bSqv89Xu1SUQ6cPLZ_881DX1G8BHoOUMm30Y7dOaMMSiooX7WPilOQXJaiUc3jHFMhSpCiOSmepXRNKTAF8LQ44ZKpSoE6LWK7jcE7S1ZdmuJsJ3eD5Ms8jMGbeEcuXEKTkFwlskgpWGcmXJNbN23J5c5t0IcRyx9ujZnse4zoJ2cG8hmn7d1gJhc8cZ68XyzJcvYb0uIwpOfFk94MCV8cz7Pi24fLr-2ncrn6eNUulqWVlE4l9jUHriwC5DuAZRU3HUJvTCeN7JE3HRpABaYGtbZoq8ZIIeqmrqlF5GdFedBNt7ibO72Lbswz6WCcPj79zBFqIYWC6r_8hfu-0CFu9DzOmlFolMj8uwOf4RFzA36KZniQ9vDHu63ehBvd5GKVkFngzVEghl8zpkmPLtm8IuMxzEnngRvGaipZRl__g16HOfq8vkzVjCtWS54peqBsDClF7O-bAar3htF7w-i9YfTBMDnl1d9D3Cf8cQj_DeA2v4Y</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Eriksson Ström, Jonas</creator><creator>Kebede Merid, Simon</creator><creator>Pourazar, Jamshid</creator><creator>Blomberg, Anders</creator><creator>Lindberg, Anne</creator><creator>Ringh, Mikael V</creator><creator>Hagemann-Jensen, Michael</creator><creator>Ekström, Tomas J</creator><creator>Behndig, Annelie F</creator><creator>Melén, Erik</creator><general>American Thoracic Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><scope>ADHXS</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>D93</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-3434-988X</orcidid><orcidid>https://orcid.org/0000-0002-3292-7471</orcidid></search><sort><creationdate>20220601</creationdate><title>Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells</title><author>Eriksson Ström, Jonas ; Kebede Merid, Simon ; Pourazar, Jamshid ; Blomberg, Anders ; Lindberg, Anne ; Ringh, Mikael V ; Hagemann-Jensen, Michael ; Ekström, Tomas J ; Behndig, Annelie F ; Melén, Erik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-ef73138ce1150011c263abe1faab5a5fe39bea1e81a718dcec69a54479770cee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aging</topic><topic>BAL cells</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Epigenome</topic><topic>Gene expression</topic><topic>Genetic diversity</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Humans</topic><topic>Lung</topic><topic>Lung diseases</topic><topic>Obstructive lung disease</topic><topic>Original Research</topic><topic>Pulmonary Disease, Chronic Obstructive - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eriksson Ström, Jonas</creatorcontrib><creatorcontrib>Kebede Merid, Simon</creatorcontrib><creatorcontrib>Pourazar, Jamshid</creatorcontrib><creatorcontrib>Blomberg, Anders</creatorcontrib><creatorcontrib>Lindberg, Anne</creatorcontrib><creatorcontrib>Ringh, Mikael V</creatorcontrib><creatorcontrib>Hagemann-Jensen, Michael</creatorcontrib><creatorcontrib>Ekström, Tomas J</creatorcontrib><creatorcontrib>Behndig, Annelie F</creatorcontrib><creatorcontrib>Melén, Erik</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Umeå universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Umeå universitet</collection><collection>SwePub Articles full text</collection><jtitle>American journal of respiratory cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eriksson Ström, Jonas</au><au>Kebede Merid, Simon</au><au>Pourazar, Jamshid</au><au>Blomberg, Anders</au><au>Lindberg, Anne</au><au>Ringh, Mikael V</au><au>Hagemann-Jensen, Michael</au><au>Ekström, Tomas J</au><au>Behndig, Annelie F</au><au>Melén, Erik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells</atitle><jtitle>American journal of respiratory cell and molecular biology</jtitle><addtitle>Am J Respir Cell Mol Biol</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>66</volume><issue>6</issue><spage>638</spage><epage>647</epage><pages>638-647</pages><issn>1044-1549</issn><issn>1535-4989</issn><eissn>1535-4989</eissn><abstract>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
) enrichment in pathways and functional gene relationships using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology,
) accelerated aging using Horvath's epigenetic clock,
) correlation with gene expression, and
) colocalization with genetic variation. We found 1,155 Bonferroni-significant (
< 6.74 × 10
) 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.</abstract><cop>United States</cop><pub>American Thoracic Society</pub><pmid>35286818</pmid><doi>10.1165/rcmb.2021-0403OC</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3434-988X</orcidid><orcidid>https://orcid.org/0000-0002-3292-7471</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1044-1549 |
| ispartof | American journal of respiratory cell and molecular biology, 2022-06, Vol.66 (6), p.638-647 |
| issn | 1044-1549 1535-4989 1535-4989 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_454816 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; SWEPUB Freely available online |
| subjects | Aging BAL cells Chronic obstructive pulmonary disease Deoxyribonucleic acid DNA DNA methylation DNA Methylation - genetics Epigenesis, Genetic Epigenetics Epigenome Gene expression Genetic diversity Genome-Wide Association Study Genomes Humans Lung Lung diseases Obstructive lung disease Original Research Pulmonary Disease, Chronic Obstructive - genetics |
| title | Chronic Obstructive Pulmonary Disease Is Associated with Epigenome-Wide Differential Methylation in BAL Lung Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T12%3A07%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chronic%20Obstructive%20Pulmonary%20Disease%20Is%20Associated%20with%20Epigenome-Wide%20Differential%20Methylation%20in%20BAL%20Lung%20Cells&rft.jtitle=American%20journal%20of%20respiratory%20cell%20and%20molecular%20biology&rft.au=Eriksson%20Str%C3%B6m,%20Jonas&rft.date=2022-06-01&rft.volume=66&rft.issue=6&rft.spage=638&rft.epage=647&rft.pages=638-647&rft.issn=1044-1549&rft.eissn=1535-4989&rft_id=info:doi/10.1165/rcmb.2021-0403OC&rft_dat=%3Cproquest_swepu%3E2639227052%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2672382753&rft_id=info:pmid/35286818&rfr_iscdi=true |