Cannabis use linked to widespread methylation changes in autism gene DLGAP2 in human sperm
Cannabis use was associated with widespread hypomethylation of the autism-linked gene DLGAP2 in human sperm, and similar changes were found in rat sperm after THC exposure and in the brains of offspring from THC-exposed fathers.
Quick Facts
What This Study Found
Using RRBS, cannabis use was associated with significant hypomethylation of the autism-linked gene DLGAP2 in human sperm. Targeted analysis confirmed differential methylation at 9 CpG sites in intron 7. DLGAP2 methylation and expression in human fetal brain tissue were inversely correlated. THC exposure in rats produced similar methylation changes in sperm, and these changes were also found in the nucleus accumbens of offspring from THC-exposed fathers.
Key Numbers
DLGAP2 hypomethylated in human sperm of cannabis users; 9 CpG sites in intron 7; methylation-expression inversely correlated in fetal brain; similar changes in rat sperm after THC; changes present in offspring nucleus accumbens.
How They Did This
RRBS of human sperm from cannabis users vs non-users, with pyrosequencing validation at DLGAP2. Cross-species validation in THC-exposed rats. DLGAP2 methylation-expression correlation in human conceptal brain tissue. Offspring brain analysis in rat model.
Why This Research Matters
This is the first demonstration of a specific gene (DLGAP2) where cannabis-associated sperm methylation changes may transmit to offspring brain tissue via the father. DLGAP2 is strongly implicated in autism and synaptic function.
The Bigger Picture
If paternal cannabis use alters epigenetic marks at autism-related genes and these marks transmit to offspring brains, it would represent a novel environmental risk factor for neurodevelopmental disorders mediated through the father.
What This Study Doesn't Tell Us
Human sperm data is cross-sectional (cannot prove causation); small human samples; rat model used different THC route than human smoking; offspring changes found in only one brain region; does not assess autism-related behavior in offspring.
Questions This Raises
- ?Does paternal cannabis use increase autism risk in children?
- ?Can these epigenetic changes be reversed by cannabis cessation before conception?
Trust & Context
- Key Stat:
- Autism gene DLGAP2 hypomethylated in human sperm of cannabis users; changes found in rat offspring brains
- Evidence Grade:
- Moderate: cross-species validation (human and rat) with mechanistic plausibility, but cross-sectional human data.
- Study Age:
- Published 2020.
- Original Title:
- Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.
- Published In:
- Epigenetics, 15(1-2), 161-173 (2020)
- Authors:
- Schrott, Rose(6), Acharya, Kelly(3), Itchon-Ramos, Nilda(3), Hawkey, Andrew B, Pippen, Erica, Mitchell, John T, Kollins, Scott H, Levin, Edward D, Murphy, Susan K
- Database ID:
- RTHC-02833
Evidence Hierarchy
A snapshot of a population at one point in time.
What do these levels mean? →Frequently Asked Questions
Could a father cannabis use contribute to autism in children?
This study found cannabis altered methylation of the autism-linked gene DLGAP2 in human sperm. In rats, similar changes appeared in offspring brain tissue after paternal THC exposure. Whether this translates to autism risk in human children is not yet known.
What is DLGAP2?
A gene involved in synapse organization and neuronal signaling that has been strongly implicated in autism spectrum disorder. Cannabis use was associated with reduced methylation of this gene in sperm, which correlated with increased gene expression in fetal brain tissue.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-02833APA
Schrott, Rose; Acharya, Kelly; Itchon-Ramos, Nilda; Hawkey, Andrew B; Pippen, Erica; Mitchell, John T; Kollins, Scott H; Levin, Edward D; Murphy, Susan K. (2020). Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.. Epigenetics, 15(1-2), 161-173. https://doi.org/10.1080/15592294.2019.1656158
MLA
Schrott, Rose, et al. "Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.." Epigenetics, 2020. https://doi.org/10.1080/15592294.2019.1656158
RethinkTHC
RethinkTHC Research Database. "Cannabis use is associated with potentially heritable widesp..." RTHC-02833. Retrieved from https://rethinkthc.com/research/schrott-2020-cannabis-use-is-associated
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.