Cannabis use is associated with potentially heritable widespread changes in autism candidate gene <i>DLGAP2</i> DNA methylation in sperm.

dc.contributor.author

Schrott, Rose

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Acharya, Kelly

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Itchon-Ramos, Nilda

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Hawkey, Andrew B

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Pippen, Erica

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Mitchell, John T

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Kollins, Scott H

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Levin, Edward D

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Murphy, Susan K

dc.date.accessioned

2023-07-01T14:04:35Z

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2023-07-01T14:04:35Z

dc.date.issued

2020-01

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2023-07-01T14:04:34Z

dc.description.abstract

Parental cannabis use has been associated with adverse neurodevelopmental outcomes in offspring, but how such phenotypes are transmitted is largely unknown. Using reduced representation bisulphite sequencing (RRBS), we recently demonstrated that cannabis use is associated with widespread DNA methylation changes in human and rat sperm. Discs-Large Associated Protein 2 (DLGAP2), involved in synapse organization, neuronal signaling, and strongly implicated in autism, exhibited significant hypomethylation (p < 0.05) at 17 CpG sites in human sperm. We successfully validated the differential methylation present in DLGAP2 for nine CpG sites located in intron seven (p < 0.05) using quantitative bisulphite pyrosequencing. Intron 7 DNA methylation and DLGAP2 expression in human conceptal brain tissue were inversely correlated (p < 0.01). Adult male rats exposed to delta-9-tetrahydrocannabinol (THC) showed differential DNA methylation at Dlgap2 in sperm (p < 0.03), as did the nucleus accumbens of rats whose fathers were exposed to THC prior to conception (p < 0.05). Altogether, these results warrant further investigation into the effects of preconception cannabis use in males and the potential effects on subsequent generations.

dc.identifier.issn

1559-2294

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1559-2308

dc.identifier.uri

https://hdl.handle.net/10161/28271

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eng

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Informa UK Limited

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Epigenetics

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10.1080/15592294.2019.1656158

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Spermatozoa

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Nucleus Accumbens

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Animals

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Humans

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Rats

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Rats, Sprague-Dawley

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Marijuana Abuse

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Nerve Tissue Proteins

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Autistic Disorder

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DNA Methylation

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CpG Islands

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Introns

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Adolescent

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Adult

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Male

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Cannabinoid Receptor Agonists

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Dronabinol

dc.title

Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.

dc.type

Journal article

duke.contributor.orcid

Acharya, Kelly|0000-0003-1891-4196

duke.contributor.orcid

Mitchell, John T|0000-0002-9586-3823

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Kollins, Scott H|0000-0001-6847-6935

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Levin, Edward D|0000-0002-5060-9602

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Murphy, Susan K|0000-0001-8298-7272

pubs.begin-page

161

pubs.end-page

173

pubs.issue

1-2

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Duke

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Nicholas School of the Environment

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School of Medicine

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Trinity College of Arts & Sciences

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Pharmacology & Cancer Biology

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Obstetrics and Gynecology

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Pathology

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Psychiatry & Behavioral Sciences

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Obstetrics and Gynecology, Reproductive Endocrinology & Fertility

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Duke Cancer Institute

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Psychology & Neuroscience

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Duke Clinical Research Institute

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Environmental Sciences and Policy

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University Institutes and Centers

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Duke Institute for Brain Sciences

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Psychiatry, Child & Family Mental Health & Community Psychiatry

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Duke Science & Society

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Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

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Psychiatry & Behavioral Sciences, Adult Psychiatry & Psychology

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Obstetrics and Gynecology, Reproductive Sciences

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Published

pubs.volume

15

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