Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells
Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like rheumatoid arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenet...
Gespeichert in:
| Veröffentlicht in: | Human molecular genetics 2017-07, Vol.26 (14), p.2803-2811 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2811 |
|---|---|
| container_issue | 14 |
| container_start_page | 2803 |
| container_title | Human molecular genetics |
| container_volume | 26 |
| creator | Julià, Antonio Absher, Devin López-Lasanta, María Palau, Nuria Pluma, Andrea Waite Jones, Lindsay Glossop, John R Farrell, William E Myers, Richard M Marsal, Sara |
| description | Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like rheumatoid arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells. CpG methylation in isolated B lymphocytes was assayed on the Illumina HumanMethylation450 BeadChip in a discovery cohort of RA patients (N = 50) and controls (N = 75). Differential methylation was observed in 64 CpG sites (q |
| doi_str_mv | 10.1093/hmg/ddx177 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1896040001</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1896040001</sourcerecordid><originalsourceid>FETCH-LOGICAL-c323t-b8882ebbe56e068d4e7d154573445a8d9ad41592448686a860bae8b54d76e55d3</originalsourceid><addsrcrecordid>eNo9kF1LwzAUhoMobk5v_AGSSxHqkuaj6aWO-QEDb_S6pM3pGmnamaRo_70dm14dDjw8vDwIXVNyT0nOlo3bLo35oVl2guaUS5KkRLFTNCe55InMiZyhixA-CaGSs-wczVLFM5HJdI7ceme30PUOkm9rAOsQ-srqaPsOhziYEfc19g0MTsfeGqx9bLyNNuCJ7qKtLQRsbF2D37-6bUfsIDZjqyMY3E4ybDv8iCto23CJzmrdBrg63gX6eFq_r16Szdvz6-phk1QsZTEplVIplCUICUQqwyEzVHCRMc6FVibXhlORp5wrqaRWkpQaVCm4ySQIYdgC3R68O99_DRBi4WzYL9Ad9EMoqMol4WQKMqF3B7TyfQge6mLnrdN-LCgp9nmLKW9xyDvBN0fvUDow_-hfT_YL3hV4hg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1896040001</pqid></control><display><type>article</type><title>Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Julià, Antonio ; Absher, Devin ; López-Lasanta, María ; Palau, Nuria ; Pluma, Andrea ; Waite Jones, Lindsay ; Glossop, John R ; Farrell, William E ; Myers, Richard M ; Marsal, Sara</creator><creatorcontrib>Julià, Antonio ; Absher, Devin ; López-Lasanta, María ; Palau, Nuria ; Pluma, Andrea ; Waite Jones, Lindsay ; Glossop, John R ; Farrell, William E ; Myers, Richard M ; Marsal, Sara</creatorcontrib><description>Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like rheumatoid arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells. CpG methylation in isolated B lymphocytes was assayed on the Illumina HumanMethylation450 BeadChip in a discovery cohort of RA patients (N = 50) and controls (N = 75). Differential methylation was observed in 64 CpG sites (q < 0.05). Six biological pathways were also differentially methylated in RA B cells. Analysis in an independent cohort of patients (N = 15) and controls (N = 15) validated the association of 10 CpG sites located on 8 genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3 and TNFRSF13C, and 2 intergenic regions. Differential methylation at the CBL signaling pathway was replicated. Using an additional case-control cohort (N = 24), the association between RA risk and CpGs cg18972751 at CD1C (P = 2.26 × 10-9) and cg03055671 at TNFSF10 (P = 1.67 × 10-8) genes was further validated. Differential methylation at genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3, TNFRSF13C and intergenic region chr10p12.31 was replicated in a cohort of systemic lupus erythematosus (SLE) patients (N = 47) and controls (N = 56). Our results highlight genes that may drive the pathogenic activity of B cells in RA and suggest shared methylation patterns with SLE.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddx177</identifier><identifier>PMID: 28475762</identifier><language>eng</language><publisher>England</publisher><subject>Aged ; Arthritis, Rheumatoid - genetics ; Arthritis, Rheumatoid - metabolism ; B-Lymphocytes - metabolism ; Case-Control Studies ; Cohort Studies ; CpG Islands - genetics ; DNA Methylation - genetics ; Epigenesis, Genetic - genetics ; Epigenomics - methods ; Female ; Genome-Wide Association Study - methods ; Humans ; Lupus Erythematosus, Systemic - genetics ; Male ; Middle Aged ; Signal Transduction</subject><ispartof>Human molecular genetics, 2017-07, Vol.26 (14), p.2803-2811</ispartof><rights>The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c323t-b8882ebbe56e068d4e7d154573445a8d9ad41592448686a860bae8b54d76e55d3</citedby><cites>FETCH-LOGICAL-c323t-b8882ebbe56e068d4e7d154573445a8d9ad41592448686a860bae8b54d76e55d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28475762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Julià, Antonio</creatorcontrib><creatorcontrib>Absher, Devin</creatorcontrib><creatorcontrib>López-Lasanta, María</creatorcontrib><creatorcontrib>Palau, Nuria</creatorcontrib><creatorcontrib>Pluma, Andrea</creatorcontrib><creatorcontrib>Waite Jones, Lindsay</creatorcontrib><creatorcontrib>Glossop, John R</creatorcontrib><creatorcontrib>Farrell, William E</creatorcontrib><creatorcontrib>Myers, Richard M</creatorcontrib><creatorcontrib>Marsal, Sara</creatorcontrib><title>Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like rheumatoid arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells. CpG methylation in isolated B lymphocytes was assayed on the Illumina HumanMethylation450 BeadChip in a discovery cohort of RA patients (N = 50) and controls (N = 75). Differential methylation was observed in 64 CpG sites (q < 0.05). Six biological pathways were also differentially methylated in RA B cells. Analysis in an independent cohort of patients (N = 15) and controls (N = 15) validated the association of 10 CpG sites located on 8 genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3 and TNFRSF13C, and 2 intergenic regions. Differential methylation at the CBL signaling pathway was replicated. Using an additional case-control cohort (N = 24), the association between RA risk and CpGs cg18972751 at CD1C (P = 2.26 × 10-9) and cg03055671 at TNFSF10 (P = 1.67 × 10-8) genes was further validated. Differential methylation at genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3, TNFRSF13C and intergenic region chr10p12.31 was replicated in a cohort of systemic lupus erythematosus (SLE) patients (N = 47) and controls (N = 56). Our results highlight genes that may drive the pathogenic activity of B cells in RA and suggest shared methylation patterns with SLE.</description><subject>Aged</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>B-Lymphocytes - metabolism</subject><subject>Case-Control Studies</subject><subject>Cohort Studies</subject><subject>CpG Islands - genetics</subject><subject>DNA Methylation - genetics</subject><subject>Epigenesis, Genetic - genetics</subject><subject>Epigenomics - methods</subject><subject>Female</subject><subject>Genome-Wide Association Study - methods</subject><subject>Humans</subject><subject>Lupus Erythematosus, Systemic - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Signal Transduction</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1LwzAUhoMobk5v_AGSSxHqkuaj6aWO-QEDb_S6pM3pGmnamaRo_70dm14dDjw8vDwIXVNyT0nOlo3bLo35oVl2guaUS5KkRLFTNCe55InMiZyhixA-CaGSs-wczVLFM5HJdI7ceme30PUOkm9rAOsQ-srqaPsOhziYEfc19g0MTsfeGqx9bLyNNuCJ7qKtLQRsbF2D37-6bUfsIDZjqyMY3E4ybDv8iCto23CJzmrdBrg63gX6eFq_r16Szdvz6-phk1QsZTEplVIplCUICUQqwyEzVHCRMc6FVibXhlORp5wrqaRWkpQaVCm4ySQIYdgC3R68O99_DRBi4WzYL9Ad9EMoqMol4WQKMqF3B7TyfQge6mLnrdN-LCgp9nmLKW9xyDvBN0fvUDow_-hfT_YL3hV4hg</recordid><startdate>20170715</startdate><enddate>20170715</enddate><creator>Julià, Antonio</creator><creator>Absher, Devin</creator><creator>López-Lasanta, María</creator><creator>Palau, Nuria</creator><creator>Pluma, Andrea</creator><creator>Waite Jones, Lindsay</creator><creator>Glossop, John R</creator><creator>Farrell, William E</creator><creator>Myers, Richard M</creator><creator>Marsal, Sara</creator><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>7X8</scope></search><sort><creationdate>20170715</creationdate><title>Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells</title><author>Julià, Antonio ; Absher, Devin ; López-Lasanta, María ; Palau, Nuria ; Pluma, Andrea ; Waite Jones, Lindsay ; Glossop, John R ; Farrell, William E ; Myers, Richard M ; Marsal, Sara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c323t-b8882ebbe56e068d4e7d154573445a8d9ad41592448686a860bae8b54d76e55d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>B-Lymphocytes - metabolism</topic><topic>Case-Control Studies</topic><topic>Cohort Studies</topic><topic>CpG Islands - genetics</topic><topic>DNA Methylation - genetics</topic><topic>Epigenesis, Genetic - genetics</topic><topic>Epigenomics - methods</topic><topic>Female</topic><topic>Genome-Wide Association Study - methods</topic><topic>Humans</topic><topic>Lupus Erythematosus, Systemic - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Julià, Antonio</creatorcontrib><creatorcontrib>Absher, Devin</creatorcontrib><creatorcontrib>López-Lasanta, María</creatorcontrib><creatorcontrib>Palau, Nuria</creatorcontrib><creatorcontrib>Pluma, Andrea</creatorcontrib><creatorcontrib>Waite Jones, Lindsay</creatorcontrib><creatorcontrib>Glossop, John R</creatorcontrib><creatorcontrib>Farrell, William E</creatorcontrib><creatorcontrib>Myers, Richard M</creatorcontrib><creatorcontrib>Marsal, Sara</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Julià, Antonio</au><au>Absher, Devin</au><au>López-Lasanta, María</au><au>Palau, Nuria</au><au>Pluma, Andrea</au><au>Waite Jones, Lindsay</au><au>Glossop, John R</au><au>Farrell, William E</au><au>Myers, Richard M</au><au>Marsal, Sara</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2017-07-15</date><risdate>2017</risdate><volume>26</volume><issue>14</issue><spage>2803</spage><epage>2811</epage><pages>2803-2811</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like rheumatoid arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells. CpG methylation in isolated B lymphocytes was assayed on the Illumina HumanMethylation450 BeadChip in a discovery cohort of RA patients (N = 50) and controls (N = 75). Differential methylation was observed in 64 CpG sites (q < 0.05). Six biological pathways were also differentially methylated in RA B cells. Analysis in an independent cohort of patients (N = 15) and controls (N = 15) validated the association of 10 CpG sites located on 8 genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3 and TNFRSF13C, and 2 intergenic regions. Differential methylation at the CBL signaling pathway was replicated. Using an additional case-control cohort (N = 24), the association between RA risk and CpGs cg18972751 at CD1C (P = 2.26 × 10-9) and cg03055671 at TNFSF10 (P = 1.67 × 10-8) genes was further validated. Differential methylation at genes CD1C, TNFSF10, PARVG, NID1, DHRS12, ITPK1, ACSF3, TNFRSF13C and intergenic region chr10p12.31 was replicated in a cohort of systemic lupus erythematosus (SLE) patients (N = 47) and controls (N = 56). Our results highlight genes that may drive the pathogenic activity of B cells in RA and suggest shared methylation patterns with SLE.</abstract><cop>England</cop><pmid>28475762</pmid><doi>10.1093/hmg/ddx177</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0964-6906 |
| ispartof | Human molecular genetics, 2017-07, Vol.26 (14), p.2803-2811 |
| issn | 0964-6906 1460-2083 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1896040001 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Aged Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - metabolism B-Lymphocytes - metabolism Case-Control Studies Cohort Studies CpG Islands - genetics DNA Methylation - genetics Epigenesis, Genetic - genetics Epigenomics - methods Female Genome-Wide Association Study - methods Humans Lupus Erythematosus, Systemic - genetics Male Middle Aged Signal Transduction |
| title | Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in B cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T19%3A06%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Epigenome-wide%20association%20study%20of%20rheumatoid%20arthritis%20identifies%20differentially%20methylated%20loci%20in%20B%20cells&rft.jtitle=Human%20molecular%20genetics&rft.au=Juli%C3%A0,%20Antonio&rft.date=2017-07-15&rft.volume=26&rft.issue=14&rft.spage=2803&rft.epage=2811&rft.pages=2803-2811&rft.issn=0964-6906&rft.eissn=1460-2083&rft_id=info:doi/10.1093/hmg/ddx177&rft_dat=%3Cproquest_cross%3E1896040001%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1896040001&rft_id=info:pmid/28475762&rfr_iscdi=true |