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
Hauptverfasser: Clark, Shaunna L., Chan, Robin, Zhao, Min, Xie, Lin Y., Copeland, William E., Aberg, Karolina A., van den Oord, Edwin J.C.G.
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container_end_page 1532
container_issue 12
container_start_page 1524
container_title Journal of the American Academy of Child and Adolescent Psychiatry
container_volume 60
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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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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