As more states legalize and decriminalize cannabis, more questions are being raised about its effects, especially on pregnancy. Now, a clear-thinking team sees through the haze and shows that maternal cannabis use during pregnancy is associated with epigenome-wide differential DNA methylation in the blood of exposed children, especially in genes involved in neurodevelopment.
Studies have shown that cannabis use can increase the risk of adverse health outcomes and accelerate epigenetic aging for those who partake. As a step toward clearing the air about pregnancy, Amy Osborne’s lab (University of Canterbury) performed epigenome-wide association studies on two longitudinal studies using DNA methylation arrays (450K and EPIC) to profile blood.
The intrepid teams looked at the data for epigenomic effects of prenatal cannabis exposure (PCE) for the Avon Longitudinal Study of Parents and Children (ALSPAC) children throughout many timepoints in their lifetimes compared to controls. Here’s what they found:
- TUBB2B, associated with the development of the cortex, is the top differentially methylated CpG in PCE children at birth
- The top one in 7 year-olds was LZTS2, which is linked to major depressive disorder
- At 15 years, the top hit was in WAC, which is associated with severe intellectual disability
- Some of the differentially methylated CpGs were shared among age groups
- Gene ontology analysis showed that many differentially methylated genes were involved in neurodevelopment, neurotransmission, and regulation of neural pathways
The Christchurch Health and Development Study (CHDS) cohorts included PCE samples and samples from children with both prenatal cannabis and tobacco exposure (PCTE). Because the sample numbers were so small for PCE and PCTE individually, the inventive team combined these groups. Here’s what they found for samples from offspring when they were 27 years old:
- Several genes involved in learning, memory, intelligence, and psychological diseases, including GRIN2D, ZNF362, and SPATA2, are differentially methylated
- Gene ontology analysis was almost an instant replay of the ALSPAC data, showing associations with genes involved in neurodevelopment and neurodevelopment disorders
Overall, the study suggests that PCE affects brain development in children through DNA methylation, though larger studies must be conducted to provide a deeper understanding.
Wave away the haze and learn more at Molecular Psychiatry, September 2024.