Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences
The impact of adolescent cannabis use is a pressing public health question owing to the high rates of use and links to negative outcomes. This study considered the association between problematic adolescent cannabis use and methylation. Using an enrichment-based sequencing approach, a methylome-wide...
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Veröffentlicht in: | Journal of the American Academy of Child and Adolescent Psychiatry 2021-12, Vol.60 (12), p.1524-1532 |
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creator | Clark, Shaunna L. Chan, Robin Zhao, Min Xie, Lin Y. Copeland, William E. Aberg, Karolina A. van den Oord, Edwin J.C.G. |
description | The impact of adolescent cannabis use is a pressing public health question owing to the high rates of use and links to negative outcomes. This study considered the association between problematic adolescent cannabis use and methylation.
Using an enrichment-based sequencing approach, a methylome-wide association study (MWAS) was performed of problematic adolescent cannabis use in 703 adolescent samples from the Great Smoky Mountain Study. Using epigenomic deconvolution, MWASs were performed for the main cell types in blood: granulocytes, T cells, B cells, and monocytes. Enrichment testing was conducted to establish overlap between cannabis-associated methylation differences and variants associated with negative mental health effects of adolescent cannabis use.
Whole-blood analyses identified 45 significant CpGs, and cell type–specific analyses yielded 32 additional CpGs not identified in the whole-blood MWAS. Significant overlap was observed between the B-cell MWAS and genetic studies of education attainment and intelligence. Furthermore, the results from both T cells and monocytes overlapped with findings from an MWAS of psychosis conducted in brain tissue.
In one of the first methylome-wide association studies of adolescent cannabis use, several methylation sites located in genes of importance for potentially relevant brain functions were identified. These findings resulted in several testable hypotheses by which cannabis-associated methylation can impact neurological development and inflammation response as well as potential mechanisms linking cannabis-associated methylation to potential downstream mental health effects. |
doi_str_mv | 10.1016/j.jaac.2021.02.008 |
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Using an enrichment-based sequencing approach, a methylome-wide association study (MWAS) was performed of problematic adolescent cannabis use in 703 adolescent samples from the Great Smoky Mountain Study. Using epigenomic deconvolution, MWASs were performed for the main cell types in blood: granulocytes, T cells, B cells, and monocytes. Enrichment testing was conducted to establish overlap between cannabis-associated methylation differences and variants associated with negative mental health effects of adolescent cannabis use.
Whole-blood analyses identified 45 significant CpGs, and cell type–specific analyses yielded 32 additional CpGs not identified in the whole-blood MWAS. Significant overlap was observed between the B-cell MWAS and genetic studies of education attainment and intelligence. Furthermore, the results from both T cells and monocytes overlapped with findings from an MWAS of psychosis conducted in brain tissue.
In one of the first methylome-wide association studies of adolescent cannabis use, several methylation sites located in genes of importance for potentially relevant brain functions were identified. These findings resulted in several testable hypotheses by which cannabis-associated methylation can impact neurological development and inflammation response as well as potential mechanisms linking cannabis-associated methylation to potential downstream mental health effects.</description><identifier>ISSN: 0890-8567</identifier><identifier>EISSN: 1527-5418</identifier><identifier>DOI: 10.1016/j.jaac.2021.02.008</identifier><identifier>PMID: 33631312</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adolescents ; Adults ; Age ; Blood ; Brain ; Cannabis ; Child development ; DNA Methylation ; Drug use ; Drug withdrawal ; Educational attainment ; Epigenetics ; Estimates ; Genes ; Genome-Wide Association Study ; Genomes ; Granulocytes ; Health status ; Humans ; Inflammation ; Information storage ; Intelligence ; Leukocytes (granulocytic) ; Lymphocytes B ; Lymphocytes T ; Marijuana ; Mental Health ; Monocytes ; Multiple Regression Analysis ; Psychosis ; Psychotic Disorders ; Public health ; Quality control ; substance use ; Variants</subject><ispartof>Journal of the American Academy of Child and Adolescent Psychiatry, 2021-12, Vol.60 (12), p.1524-1532</ispartof><rights>2021 American Academy of Child and Adolescent Psychiatry</rights><rights>Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.</rights><rights>2021. American Academy of Child and Adolescent Psychiatry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-df927c28b3a2b5f6be923340ef735abbe812829d58c72d47dcb855cf481112f33</citedby><cites>FETCH-LOGICAL-c483t-df927c28b3a2b5f6be923340ef735abbe812829d58c72d47dcb855cf481112f33</cites><orcidid>0000-0002-1348-7781 ; 0000-0001-6103-5168 ; 0000-0002-3193-6923 ; 0000-0001-5425-1356</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaac.2021.02.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,30999,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33631312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Clark, Shaunna L.</creatorcontrib><creatorcontrib>Chan, Robin</creatorcontrib><creatorcontrib>Zhao, Min</creatorcontrib><creatorcontrib>Xie, Lin Y.</creatorcontrib><creatorcontrib>Copeland, William E.</creatorcontrib><creatorcontrib>Aberg, Karolina A.</creatorcontrib><creatorcontrib>van den Oord, Edwin J.C.G.</creatorcontrib><title>Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences</title><title>Journal of the American Academy of Child and Adolescent Psychiatry</title><addtitle>J Am Acad Child Adolesc Psychiatry</addtitle><description>The impact of adolescent cannabis use is a pressing public health question owing to the high rates of use and links to negative outcomes. This study considered the association between problematic adolescent cannabis use and methylation.
Using an enrichment-based sequencing approach, a methylome-wide association study (MWAS) was performed of problematic adolescent cannabis use in 703 adolescent samples from the Great Smoky Mountain Study. Using epigenomic deconvolution, MWASs were performed for the main cell types in blood: granulocytes, T cells, B cells, and monocytes. Enrichment testing was conducted to establish overlap between cannabis-associated methylation differences and variants associated with negative mental health effects of adolescent cannabis use.
Whole-blood analyses identified 45 significant CpGs, and cell type–specific analyses yielded 32 additional CpGs not identified in the whole-blood MWAS. Significant overlap was observed between the B-cell MWAS and genetic studies of education attainment and intelligence. Furthermore, the results from both T cells and monocytes overlapped with findings from an MWAS of psychosis conducted in brain tissue.
In one of the first methylome-wide association studies of adolescent cannabis use, several methylation sites located in genes of importance for potentially relevant brain functions were identified. These findings resulted in several testable hypotheses by which cannabis-associated methylation can impact neurological development and inflammation response as well as potential mechanisms linking cannabis-associated methylation to potential downstream mental health effects.</description><subject>Adolescent</subject><subject>Adolescents</subject><subject>Adults</subject><subject>Age</subject><subject>Blood</subject><subject>Brain</subject><subject>Cannabis</subject><subject>Child development</subject><subject>DNA Methylation</subject><subject>Drug use</subject><subject>Drug withdrawal</subject><subject>Educational attainment</subject><subject>Epigenetics</subject><subject>Estimates</subject><subject>Genes</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Granulocytes</subject><subject>Health status</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Information storage</subject><subject>Intelligence</subject><subject>Leukocytes (granulocytic)</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Marijuana</subject><subject>Mental Health</subject><subject>Monocytes</subject><subject>Multiple Regression Analysis</subject><subject>Psychosis</subject><subject>Psychotic Disorders</subject><subject>Public health</subject><subject>Quality control</subject><subject>substance use</subject><subject>Variants</subject><issn>0890-8567</issn><issn>1527-5418</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>7QJ</sourceid><recordid>eNp9kUtr3DAUhUVpaaZp_0AXRdBNNnakKz9kKIUwtMlAHl00ayHL1xm5tpRKnoH8-8pMEtosuhIXffdwzj2EfOQs54xXp0M-aG1yYMBzBjlj8hVZ8RLqrCy4fE1WTDYsk2VVH5F3MQ6MMV5L-ZYcCVEJLjisyK8rnLcPo5-soRu3xzjbOz1b76jv6Y_g2xGnNBt61vkRo0E307V2Trc20tuIVLuObuZIr3HZ2yO9Soge6QXqcd7StXcRf-_QGYzvyZtejxE_PL7H5Pb7t5_ri-zy5nyzPrvMTCHFnHV9A7UB2QoNbdlXLTYgRMGwr0Wp2xYlBwlNV0pTQ1fUnWllWZq-kJxz6IU4Jl8Puve7dsJu8Rz0qO6DnXR4UF5b9e-Ps1t15_dKCsmggiRw8igQfPIeZzXZFH0ctUO_iwqKpoBGNKxM6OcX6OB3waV4CmSR7l9XBUsUHCgTfIwB-2cznKmlSzWopUu1dKkYqNRlWvr0d4znlafyEvDlAGA65t5iUNHY5dKdDWhm1Xn7P_0_89axSw</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Clark, Shaunna L.</creator><creator>Chan, Robin</creator><creator>Zhao, Min</creator><creator>Xie, Lin Y.</creator><creator>Copeland, William E.</creator><creator>Aberg, Karolina A.</creator><creator>van den Oord, Edwin J.C.G.</creator><general>Elsevier Inc</general><general>Elsevier BV</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>7QJ</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1348-7781</orcidid><orcidid>https://orcid.org/0000-0001-6103-5168</orcidid><orcidid>https://orcid.org/0000-0002-3193-6923</orcidid><orcidid>https://orcid.org/0000-0001-5425-1356</orcidid></search><sort><creationdate>20211201</creationdate><title>Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences</title><author>Clark, Shaunna L. ; Chan, Robin ; Zhao, Min ; Xie, Lin Y. ; Copeland, William E. ; Aberg, Karolina A. ; van den Oord, Edwin J.C.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-df927c28b3a2b5f6be923340ef735abbe812829d58c72d47dcb855cf481112f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adolescents</topic><topic>Adults</topic><topic>Age</topic><topic>Blood</topic><topic>Brain</topic><topic>Cannabis</topic><topic>Child development</topic><topic>DNA Methylation</topic><topic>Drug use</topic><topic>Drug withdrawal</topic><topic>Educational attainment</topic><topic>Epigenetics</topic><topic>Estimates</topic><topic>Genes</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Granulocytes</topic><topic>Health status</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Information storage</topic><topic>Intelligence</topic><topic>Leukocytes (granulocytic)</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Marijuana</topic><topic>Mental Health</topic><topic>Monocytes</topic><topic>Multiple Regression Analysis</topic><topic>Psychosis</topic><topic>Psychotic Disorders</topic><topic>Public health</topic><topic>Quality control</topic><topic>substance use</topic><topic>Variants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clark, Shaunna L.</creatorcontrib><creatorcontrib>Chan, Robin</creatorcontrib><creatorcontrib>Zhao, Min</creatorcontrib><creatorcontrib>Xie, Lin Y.</creatorcontrib><creatorcontrib>Copeland, William E.</creatorcontrib><creatorcontrib>Aberg, Karolina A.</creatorcontrib><creatorcontrib>van den Oord, Edwin J.C.G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Academy of Child and Adolescent Psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clark, Shaunna L.</au><au>Chan, Robin</au><au>Zhao, Min</au><au>Xie, Lin Y.</au><au>Copeland, William E.</au><au>Aberg, Karolina A.</au><au>van den Oord, Edwin J.C.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences</atitle><jtitle>Journal of the American Academy of Child and Adolescent Psychiatry</jtitle><addtitle>J Am Acad Child Adolesc Psychiatry</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>60</volume><issue>12</issue><spage>1524</spage><epage>1532</epage><pages>1524-1532</pages><issn>0890-8567</issn><eissn>1527-5418</eissn><abstract>The impact of adolescent cannabis use is a pressing public health question owing to the high rates of use and links to negative outcomes. This study considered the association between problematic adolescent cannabis use and methylation.
Using an enrichment-based sequencing approach, a methylome-wide association study (MWAS) was performed of problematic adolescent cannabis use in 703 adolescent samples from the Great Smoky Mountain Study. Using epigenomic deconvolution, MWASs were performed for the main cell types in blood: granulocytes, T cells, B cells, and monocytes. Enrichment testing was conducted to establish overlap between cannabis-associated methylation differences and variants associated with negative mental health effects of adolescent cannabis use.
Whole-blood analyses identified 45 significant CpGs, and cell type–specific analyses yielded 32 additional CpGs not identified in the whole-blood MWAS. Significant overlap was observed between the B-cell MWAS and genetic studies of education attainment and intelligence. Furthermore, the results from both T cells and monocytes overlapped with findings from an MWAS of psychosis conducted in brain tissue.
In one of the first methylome-wide association studies of adolescent cannabis use, several methylation sites located in genes of importance for potentially relevant brain functions were identified. These findings resulted in several testable hypotheses by which cannabis-associated methylation can impact neurological development and inflammation response as well as potential mechanisms linking cannabis-associated methylation to potential downstream mental health effects.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33631312</pmid><doi>10.1016/j.jaac.2021.02.008</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1348-7781</orcidid><orcidid>https://orcid.org/0000-0001-6103-5168</orcidid><orcidid>https://orcid.org/0000-0002-3193-6923</orcidid><orcidid>https://orcid.org/0000-0001-5425-1356</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adolescents Adults Age Blood Brain Cannabis Child development DNA Methylation Drug use Drug withdrawal Educational attainment Epigenetics Estimates Genes Genome-Wide Association Study Genomes Granulocytes Health status Humans Inflammation Information storage Intelligence Leukocytes (granulocytic) Lymphocytes B Lymphocytes T Marijuana Mental Health Monocytes Multiple Regression Analysis Psychosis Psychotic Disorders Public health Quality control substance use Variants |
title | Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences |
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