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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Schrott, R; Acharya, K; Itchon-Ramos, N; Hawkey, AB; Pippen, E; Mitchell, JT; Kollins, SH; Levin, ED; Murphy, SK

Published Date

  • January 2020

Published In

Volume / Issue

  • 15 / 1-2

Start / End Page

  • 161 - 173

PubMed ID

  • 31451081

Pubmed Central ID

  • 31451081

Electronic International Standard Serial Number (EISSN)

  • 1559-2308

Digital Object Identifier (DOI)

  • 10.1080/15592294.2019.1656158

Language

  • eng

Conference Location

  • United States