Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.
Rose SchrottKelly AcharyaNilda Itchon-RamosAndrew B HawkeyErica PippenJohn T MitchellScott H KollinsEdward D LevinSusan K MurphyPublished in: Epigenetics (2019)
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.
Keyphrases
- dna methylation
- genome wide
- endothelial cells
- gene expression
- induced pluripotent stem cells
- copy number
- autism spectrum disorder
- intellectual disability
- pluripotent stem cells
- poor prognosis
- oxidative stress
- young adults
- high resolution
- skeletal muscle
- resting state
- climate change
- childhood cancer
- weight loss
- functional connectivity