Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human...
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| Veröffentlicht in: | Molecular psychiatry 2021-08, Vol.26 (8), p.4367-4382 |
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| creator | Meng, Weida Sjöholm, Louise K. Kononenko, Olga Tay, Nicole Zhang, Dandan Sarkisyan, Daniil Geske, Jennifer R. Ing, Alex Qiu, Wenqing Watanabe, Hiroyuki Almamoun, Radwa Frieling, Helge Bleich, Stefan Cui, Donghong Biernacka, Joanna M. Mayfield, R. Dayne Dang, Yongjun Karpyak, Victor M. Schumann, Gunter Bakalkin, Georgy Ekström, Tomas J. Rüegg, Joelle Liu, Yun |
| description | Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and
Dlgap2
-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that
DLGAP2
may be an interface for genetic and epigenetic factors controlling alcohol use and dependence. |
| doi_str_mv | 10.1038/s41380-019-0588-9 |
| format | Article |
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Dlgap2
-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that
DLGAP2
may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.</description><identifier>ISSN: 1359-4184</identifier><identifier>ISSN: 1476-5578</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-019-0588-9</identifier><identifier>PMID: 31745236</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/43 ; 45/61 ; 59/57 ; 631/208 ; 631/337 ; 64/60 ; 692/699/476/5 ; Alcohol Drinking - genetics ; Alcohol use ; Alcoholism ; Alcoholism - genetics ; Animals ; Association analysis ; Behavioral Sciences ; Biological Psychology ; Brain ; DNA Methylation ; Drug dependence ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Epigenome ; Gene expression ; Genetic aspects ; Genotype ; Genotypes ; Health aspects ; Medicine ; Medicine & Public Health ; Methylation ; Mice ; Nerve Tissue Proteins - genetics ; Neurosciences ; Pharmacotherapy ; Physiological aspects ; Psychiatry ; Public health ; Reinforcement ; Risk factors</subject><ispartof>Molecular psychiatry, 2021-08, Vol.26 (8), p.4367-4382</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>2019. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-169a48aeedbd4b6b60c42998dbc50fae15f31411e17e0847c00ab81c250c5f733</citedby><cites>FETCH-LOGICAL-c514t-169a48aeedbd4b6b60c42998dbc50fae15f31411e17e0847c00ab81c250c5f733</cites><orcidid>0000-0001-5753-1265 ; 0000-0002-7740-6469 ; 0000-0001-9350-4440 ; 0000-0002-3747-1581 ; 0000-0002-7341-1535 ; 0000-0002-1307-408X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41380-019-0588-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41380-019-0588-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31745236$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-466959$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:148611644$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Meng, Weida</creatorcontrib><creatorcontrib>Sjöholm, Louise K.</creatorcontrib><creatorcontrib>Kononenko, Olga</creatorcontrib><creatorcontrib>Tay, Nicole</creatorcontrib><creatorcontrib>Zhang, Dandan</creatorcontrib><creatorcontrib>Sarkisyan, Daniil</creatorcontrib><creatorcontrib>Geske, Jennifer R.</creatorcontrib><creatorcontrib>Ing, Alex</creatorcontrib><creatorcontrib>Qiu, Wenqing</creatorcontrib><creatorcontrib>Watanabe, Hiroyuki</creatorcontrib><creatorcontrib>Almamoun, Radwa</creatorcontrib><creatorcontrib>Frieling, Helge</creatorcontrib><creatorcontrib>Bleich, Stefan</creatorcontrib><creatorcontrib>Cui, Donghong</creatorcontrib><creatorcontrib>Biernacka, Joanna M.</creatorcontrib><creatorcontrib>Mayfield, R. Dayne</creatorcontrib><creatorcontrib>Dang, Yongjun</creatorcontrib><creatorcontrib>Karpyak, Victor M.</creatorcontrib><creatorcontrib>Schumann, Gunter</creatorcontrib><creatorcontrib>Bakalkin, Georgy</creatorcontrib><creatorcontrib>Ekström, Tomas J.</creatorcontrib><creatorcontrib>Rüegg, Joelle</creatorcontrib><creatorcontrib>Liu, Yun</creatorcontrib><creatorcontrib>IMAGEN Consortium</creatorcontrib><title>Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and
Dlgap2
-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that
DLGAP2
may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.</description><subject>45/43</subject><subject>45/61</subject><subject>59/57</subject><subject>631/208</subject><subject>631/337</subject><subject>64/60</subject><subject>692/699/476/5</subject><subject>Alcohol Drinking - genetics</subject><subject>Alcohol use</subject><subject>Alcoholism</subject><subject>Alcoholism - genetics</subject><subject>Animals</subject><subject>Association analysis</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Brain</subject><subject>DNA Methylation</subject><subject>Drug dependence</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Epigenome</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Health aspects</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylation</subject><subject>Mice</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Neurosciences</subject><subject>Pharmacotherapy</subject><subject>Physiological aspects</subject><subject>Psychiatry</subject><subject>Public health</subject><subject>Reinforcement</subject><subject>Risk factors</subject><issn>1359-4184</issn><issn>1476-5578</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1r3DAQhk1padK0P6CXYug1SjTWh-Xjko9tYSE5tL0KWR67Sr2SK9mE_Pto2U1CoUEHDTPPO8zMWxSfgZ4BZeo8cWCKEgoNoUIp0rwpjoHXkghRq7c5ZqIhHBQ_Kj6kdEfprijeF0cMai4qJo-L2zX6MD9MSDqc0Hfo5xInN6DH2dky4rCMZnbBl6EvLzfr1W1VOl-a0YbfYSyXhKXxXfkktvixeNebMeGnw39S_Ly--nHxjWxu1t8vVhtiBfCZgGwMVwaxazveylZSy6umUV1rBe0NgugZcACEGqnitaXUtApsJagVfc3YSUH2fdM9Tkurp-i2Jj7oYJw-pP7kCDWvhahU5k9f5S_dr5UOcdDLormUjWgy_nWPTzH8XTDN-i4s0eeNdCWUlLVgoF6owYyone_DHI3dumT1SirKWQ2CZursP1R-HW6dDR57l_P_CGAvsDGkFLF_nhao3jmv987r7LzeOa93A385DLy0W-yeFU9WZ6A6HCCX_IDxZaPXuz4CqbK3Hw</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Meng, Weida</creator><creator>Sjöholm, Louise K.</creator><creator>Kononenko, Olga</creator><creator>Tay, Nicole</creator><creator>Zhang, Dandan</creator><creator>Sarkisyan, Daniil</creator><creator>Geske, Jennifer R.</creator><creator>Ing, Alex</creator><creator>Qiu, Wenqing</creator><creator>Watanabe, Hiroyuki</creator><creator>Almamoun, Radwa</creator><creator>Frieling, Helge</creator><creator>Bleich, Stefan</creator><creator>Cui, Donghong</creator><creator>Biernacka, Joanna M.</creator><creator>Mayfield, R. 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Dayne</au><au>Dang, Yongjun</au><au>Karpyak, Victor M.</au><au>Schumann, Gunter</au><au>Bakalkin, Georgy</au><au>Ekström, Tomas J.</au><au>Rüegg, Joelle</au><au>Liu, Yun</au><aucorp>IMAGEN Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>26</volume><issue>8</issue><spage>4367</spage><epage>4382</epage><pages>4367-4382</pages><issn>1359-4184</issn><issn>1476-5578</issn><eissn>1476-5578</eissn><abstract>Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and
Dlgap2
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DLGAP2
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| ispartof | Molecular psychiatry, 2021-08, Vol.26 (8), p.4367-4382 |
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| subjects | 45/43 45/61 59/57 631/208 631/337 64/60 692/699/476/5 Alcohol Drinking - genetics Alcohol use Alcoholism Alcoholism - genetics Animals Association analysis Behavioral Sciences Biological Psychology Brain DNA Methylation Drug dependence Epigenesis, Genetic Epigenetic inheritance Epigenetics Epigenome Gene expression Genetic aspects Genotype Genotypes Health aspects Medicine Medicine & Public Health Methylation Mice Nerve Tissue Proteins - genetics Neurosciences Pharmacotherapy Physiological aspects Psychiatry Public health Reinforcement Risk factors |
| title | Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence |
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