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Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage
Little is known about the epigenetic changes associated with delayed cerebral ischemia (DCI) pathogenesis after subarachnoid hemorrhage (SAH). Here, we investigated genome-wide DNA methylation profiles specifically associated with DCI, which is a major contributor to poor clinical outcomes. An epige...
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| Published in: | Scientific reports 2020-07, Vol.10 (1), p.11419-11419, Article 11419 |
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| description | Little is known about the epigenetic changes associated with delayed cerebral ischemia (DCI) pathogenesis after subarachnoid hemorrhage (SAH). Here, we investigated genome-wide DNA methylation profiles specifically associated with DCI, which is a major contributor to poor clinical outcomes. An epigenome-wide association study (EWAS) and quantitative real-time PCR (qRT-PCR) were conducted in 40 SAH patients (DCI, n = 13; non-DCI, n = 27). A replication study using bisulfite modification and methylation-specific PCR was further performed in 36 patients (DCI, n = 12; non-DCI, n = 24). The relative degree of methylation was described as the median and 25th–75th percentile. No significant differences in clinical characteristics between DCI and non-DCI groups were observed. Among the top 10 differentially methylated genes analyzed via EWAS, two aberrantly methylated CpG sites of cg00441765 (
INSR
gene) and cg11464053 (
CDHR5
gene) were associated with decreased mRNA expression (2
−ΔCt
). They include
INSR
[0.00020 (0.00012–0.00030) in DCI vs. 0.00050 (0.00030–0.00068) in non-DCI] and
CDHR5
[0.114 (0.053–0.143) in DCI vs. 0.170 (0.110–0.212) in non-DCI]. Compared with non-DCI cases, patients with DCI exhibited an increased degree of methylation in the replication study:
INSR
, 0.855 (0.779–0.913) in DCI vs. 0.582 (0.565–0.689) in non-DCI;
CDHR5
, 0.786 (0.708–0.904) in DCI vs. 0.632 (0.610–0.679) in non-DCI. Hypermethylation of two novel genes,
INSR
and
CDHR5
may serve as a biomarker for early detection of DCI following SAH. |
| doi_str_mv | 10.1038/s41598-020-68325-3 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7351711</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2423068259</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-d40ff2355aae42536edd21427fc46d5b172a842bccc5baf8e29e9c4fa9ca81a03</originalsourceid><addsrcrecordid>eNp9kc1u1TAQhSNERavSF2CBLLFhE7DHdn42SFWBglTRTVlbE3ty4yqJL3bS6r49bm9bCgu8seX55viMT1G8EfyD4LL5mJTQbVNy4GXVSNClfFEcAVe6BAnw8tn5sDhJ6ZrnpaFVon1VHEqotFCVPCrSOc1hovLWO2LdGIJjn3-csomWYTfi4sPMcMZxl3xifmbbfEXzktitXwbmaMQdOWYpUhdxZD7ZgSaPDPuFIktrhxHtMAfvWC6EGAfc0OvioMcx0cnDflz8_Prl6uxbeXF5_v3s9KK0qlZL6RTve5BaI5ICLStyDoSCureqcroTNWCjoLPW6g77hqCl1qoeW4uNQC6Pi0973e3aTeRsNp5Nmm30E8adCejN35XZD2YTbkwttaiFyALvHwRi-LVSWsyUJ6RxxJnCmgwokLxqQLcZffcPeh3WmH_ungIugOs7QdhTNoaUIvVPZgQ3d7Gafawmx2ruYzUyN719PsZTy2OIGZB7IOXSvKH45-3_yP4G9JiwVw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2422012051</pqid></control><display><type>article</type><title>Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Kim, Bong Jun ; Kim, Youngmi ; Youn, Dong Hyuk ; Park, Jeong Jin ; Rhim, Jong Kook ; Kim, Heung Cheol ; Kang, Keunsoo ; Jeon, Jin Pyeong</creator><creatorcontrib>Kim, Bong Jun ; Kim, Youngmi ; Youn, Dong Hyuk ; Park, Jeong Jin ; Rhim, Jong Kook ; Kim, Heung Cheol ; Kang, Keunsoo ; Jeon, Jin Pyeong</creatorcontrib><description>Little is known about the epigenetic changes associated with delayed cerebral ischemia (DCI) pathogenesis after subarachnoid hemorrhage (SAH). Here, we investigated genome-wide DNA methylation profiles specifically associated with DCI, which is a major contributor to poor clinical outcomes. An epigenome-wide association study (EWAS) and quantitative real-time PCR (qRT-PCR) were conducted in 40 SAH patients (DCI, n = 13; non-DCI, n = 27). A replication study using bisulfite modification and methylation-specific PCR was further performed in 36 patients (DCI, n = 12; non-DCI, n = 24). The relative degree of methylation was described as the median and 25th–75th percentile. No significant differences in clinical characteristics between DCI and non-DCI groups were observed. Among the top 10 differentially methylated genes analyzed via EWAS, two aberrantly methylated CpG sites of cg00441765 (
INSR
gene) and cg11464053 (
CDHR5
gene) were associated with decreased mRNA expression (2
−ΔCt
). They include
INSR
[0.00020 (0.00012–0.00030) in DCI vs. 0.00050 (0.00030–0.00068) in non-DCI] and
CDHR5
[0.114 (0.053–0.143) in DCI vs. 0.170 (0.110–0.212) in non-DCI]. Compared with non-DCI cases, patients with DCI exhibited an increased degree of methylation in the replication study:
INSR
, 0.855 (0.779–0.913) in DCI vs. 0.582 (0.565–0.689) in non-DCI;
CDHR5
, 0.786 (0.708–0.904) in DCI vs. 0.632 (0.610–0.679) in non-DCI. Hypermethylation of two novel genes,
INSR
and
CDHR5
may serve as a biomarker for early detection of DCI following SAH.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-68325-3</identifier><identifier>PMID: 32651463</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/308 ; 692/617 ; Adult ; Aged ; Antigens, CD - genetics ; Biomarkers ; Bisulfite ; Brain Ischemia - genetics ; Cadherins - genetics ; CpG Islands ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Epigenesis, Genetic ; Epigenome ; Female ; Gene expression ; Genes ; Genome-Wide Association Study ; Genomes ; Humanities and Social Sciences ; Humans ; Ischemia ; Male ; Middle Aged ; multidisciplinary ; Polymerase chain reaction ; Real-Time Polymerase Chain Reaction ; Receptor, Insulin - genetics ; Replication ; RNA, Messenger - genetics ; Science ; Science (multidisciplinary) ; Stroke ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - genetics ; Vasospasm, Intracranial - complications</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.11419-11419, Article 11419</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-d40ff2355aae42536edd21427fc46d5b172a842bccc5baf8e29e9c4fa9ca81a03</citedby><cites>FETCH-LOGICAL-c474t-d40ff2355aae42536edd21427fc46d5b172a842bccc5baf8e29e9c4fa9ca81a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2422012051/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2422012051?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32651463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Bong Jun</creatorcontrib><creatorcontrib>Kim, Youngmi</creatorcontrib><creatorcontrib>Youn, Dong Hyuk</creatorcontrib><creatorcontrib>Park, Jeong Jin</creatorcontrib><creatorcontrib>Rhim, Jong Kook</creatorcontrib><creatorcontrib>Kim, Heung Cheol</creatorcontrib><creatorcontrib>Kang, Keunsoo</creatorcontrib><creatorcontrib>Jeon, Jin Pyeong</creatorcontrib><title>Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Little is known about the epigenetic changes associated with delayed cerebral ischemia (DCI) pathogenesis after subarachnoid hemorrhage (SAH). Here, we investigated genome-wide DNA methylation profiles specifically associated with DCI, which is a major contributor to poor clinical outcomes. An epigenome-wide association study (EWAS) and quantitative real-time PCR (qRT-PCR) were conducted in 40 SAH patients (DCI, n = 13; non-DCI, n = 27). A replication study using bisulfite modification and methylation-specific PCR was further performed in 36 patients (DCI, n = 12; non-DCI, n = 24). The relative degree of methylation was described as the median and 25th–75th percentile. No significant differences in clinical characteristics between DCI and non-DCI groups were observed. Among the top 10 differentially methylated genes analyzed via EWAS, two aberrantly methylated CpG sites of cg00441765 (
INSR
gene) and cg11464053 (
CDHR5
gene) were associated with decreased mRNA expression (2
−ΔCt
). They include
INSR
[0.00020 (0.00012–0.00030) in DCI vs. 0.00050 (0.00030–0.00068) in non-DCI] and
CDHR5
[0.114 (0.053–0.143) in DCI vs. 0.170 (0.110–0.212) in non-DCI]. Compared with non-DCI cases, patients with DCI exhibited an increased degree of methylation in the replication study:
INSR
, 0.855 (0.779–0.913) in DCI vs. 0.582 (0.565–0.689) in non-DCI;
CDHR5
, 0.786 (0.708–0.904) in DCI vs. 0.632 (0.610–0.679) in non-DCI. Hypermethylation of two novel genes,
INSR
and
CDHR5
may serve as a biomarker for early detection of DCI following SAH.</description><subject>692/308</subject><subject>692/617</subject><subject>Adult</subject><subject>Aged</subject><subject>Antigens, CD - genetics</subject><subject>Biomarkers</subject><subject>Bisulfite</subject><subject>Brain Ischemia - genetics</subject><subject>Cadherins - genetics</subject><subject>CpG Islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenome</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Male</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Polymerase chain reaction</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptor, Insulin - genetics</subject><subject>Replication</subject><subject>RNA, Messenger - genetics</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stroke</subject><subject>Subarachnoid hemorrhage</subject><subject>Subarachnoid Hemorrhage - genetics</subject><subject>Vasospasm, Intracranial - complications</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp9kc1u1TAQhSNERavSF2CBLLFhE7DHdn42SFWBglTRTVlbE3ty4yqJL3bS6r49bm9bCgu8seX55viMT1G8EfyD4LL5mJTQbVNy4GXVSNClfFEcAVe6BAnw8tn5sDhJ6ZrnpaFVon1VHEqotFCVPCrSOc1hovLWO2LdGIJjn3-csomWYTfi4sPMcMZxl3xifmbbfEXzktitXwbmaMQdOWYpUhdxZD7ZgSaPDPuFIktrhxHtMAfvWC6EGAfc0OvioMcx0cnDflz8_Prl6uxbeXF5_v3s9KK0qlZL6RTve5BaI5ICLStyDoSCureqcroTNWCjoLPW6g77hqCl1qoeW4uNQC6Pi0973e3aTeRsNp5Nmm30E8adCejN35XZD2YTbkwttaiFyALvHwRi-LVSWsyUJ6RxxJnCmgwokLxqQLcZffcPeh3WmH_ungIugOs7QdhTNoaUIvVPZgQ3d7Gafawmx2ruYzUyN719PsZTy2OIGZB7IOXSvKH45-3_yP4G9JiwVw</recordid><startdate>20200710</startdate><enddate>20200710</enddate><creator>Kim, Bong Jun</creator><creator>Kim, Youngmi</creator><creator>Youn, Dong Hyuk</creator><creator>Park, Jeong Jin</creator><creator>Rhim, Jong Kook</creator><creator>Kim, Heung Cheol</creator><creator>Kang, Keunsoo</creator><creator>Jeon, Jin Pyeong</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200710</creationdate><title>Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage</title><author>Kim, Bong Jun ; Kim, Youngmi ; Youn, Dong Hyuk ; Park, Jeong Jin ; Rhim, Jong Kook ; Kim, Heung Cheol ; Kang, Keunsoo ; Jeon, Jin Pyeong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-d40ff2355aae42536edd21427fc46d5b172a842bccc5baf8e29e9c4fa9ca81a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>692/308</topic><topic>692/617</topic><topic>Adult</topic><topic>Aged</topic><topic>Antigens, CD - genetics</topic><topic>Biomarkers</topic><topic>Bisulfite</topic><topic>Brain Ischemia - genetics</topic><topic>Cadherins - genetics</topic><topic>CpG Islands</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenome</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Ischemia</topic><topic>Male</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Polymerase chain reaction</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptor, Insulin - genetics</topic><topic>Replication</topic><topic>RNA, Messenger - genetics</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stroke</topic><topic>Subarachnoid hemorrhage</topic><topic>Subarachnoid Hemorrhage - genetics</topic><topic>Vasospasm, Intracranial - complications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Bong Jun</creatorcontrib><creatorcontrib>Kim, Youngmi</creatorcontrib><creatorcontrib>Youn, Dong Hyuk</creatorcontrib><creatorcontrib>Park, Jeong Jin</creatorcontrib><creatorcontrib>Rhim, Jong Kook</creatorcontrib><creatorcontrib>Kim, Heung Cheol</creatorcontrib><creatorcontrib>Kang, Keunsoo</creatorcontrib><creatorcontrib>Jeon, Jin Pyeong</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Bong Jun</au><au>Kim, Youngmi</au><au>Youn, Dong Hyuk</au><au>Park, Jeong Jin</au><au>Rhim, Jong Kook</au><au>Kim, Heung Cheol</au><au>Kang, Keunsoo</au><au>Jeon, Jin Pyeong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-10</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>11419</spage><epage>11419</epage><pages>11419-11419</pages><artnum>11419</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Little is known about the epigenetic changes associated with delayed cerebral ischemia (DCI) pathogenesis after subarachnoid hemorrhage (SAH). Here, we investigated genome-wide DNA methylation profiles specifically associated with DCI, which is a major contributor to poor clinical outcomes. An epigenome-wide association study (EWAS) and quantitative real-time PCR (qRT-PCR) were conducted in 40 SAH patients (DCI, n = 13; non-DCI, n = 27). A replication study using bisulfite modification and methylation-specific PCR was further performed in 36 patients (DCI, n = 12; non-DCI, n = 24). The relative degree of methylation was described as the median and 25th–75th percentile. No significant differences in clinical characteristics between DCI and non-DCI groups were observed. Among the top 10 differentially methylated genes analyzed via EWAS, two aberrantly methylated CpG sites of cg00441765 (
INSR
gene) and cg11464053 (
CDHR5
gene) were associated with decreased mRNA expression (2
−ΔCt
). They include
INSR
[0.00020 (0.00012–0.00030) in DCI vs. 0.00050 (0.00030–0.00068) in non-DCI] and
CDHR5
[0.114 (0.053–0.143) in DCI vs. 0.170 (0.110–0.212) in non-DCI]. Compared with non-DCI cases, patients with DCI exhibited an increased degree of methylation in the replication study:
INSR
, 0.855 (0.779–0.913) in DCI vs. 0.582 (0.565–0.689) in non-DCI;
CDHR5
, 0.786 (0.708–0.904) in DCI vs. 0.632 (0.610–0.679) in non-DCI. Hypermethylation of two novel genes,
INSR
and
CDHR5
may serve as a biomarker for early detection of DCI following SAH.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32651463</pmid><doi>10.1038/s41598-020-68325-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-07, Vol.10 (1), p.11419-11419, Article 11419 |
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| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 692/308 692/617 Adult Aged Antigens, CD - genetics Biomarkers Bisulfite Brain Ischemia - genetics Cadherins - genetics CpG Islands Deoxyribonucleic acid DNA DNA Methylation Epigenesis, Genetic Epigenome Female Gene expression Genes Genome-Wide Association Study Genomes Humanities and Social Sciences Humans Ischemia Male Middle Aged multidisciplinary Polymerase chain reaction Real-Time Polymerase Chain Reaction Receptor, Insulin - genetics Replication RNA, Messenger - genetics Science Science (multidisciplinary) Stroke Subarachnoid hemorrhage Subarachnoid Hemorrhage - genetics Vasospasm, Intracranial - complications |
| title | Genome-wide blood DNA methylation analysis in patients with delayed cerebral ischemia after subarachnoid hemorrhage |
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