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

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.

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Citation

Published Version (Please cite this version)

10.1080/15592294.2019.1656158

Publication Info

Schrott, Rose, Kelly Acharya, Nilda Itchon-Ramos, Andrew B Hawkey, Erica Pippen, John T Mitchell, Scott H Kollins, Edward D Levin, et al. (2020). Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm. Epigenetics, 15(1-2). pp. 161–173. 10.1080/15592294.2019.1656158 Retrieved from https://hdl.handle.net/10161/28271.

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Scholars@Duke

Acharya

Kelly S Acharya

Assistant Professor of Obstetrics and Gynecology
Mitchell

John T Mitchell

Associate Professor in Psychiatry and Behavioral Sciences
Kollins

Scott Haden Kollins

Adjunct Professor in the Department of Psychiatry and Behavioral Sciences

Scott H. Kollins, PhD received his undergraduate degree in psychology from Duke and his Master’s and Doctorate degrees in Clinical Psychology from Auburn University. After completing his clinical internship at the University of Mississippi Medical Center, where he served as Chief Intern, he joined the faculty of the Department of Psychology at Western Michigan University for three years, before joining the Duke faculty in 2000. Dr. Kollins has published more than 125 scientific papers in peer-reviewed journals.  Over the past 10 years, his research has been supported by 6 different federal agencies, including NICHD, NIDA, NIMH, NIEHS, NINDS, and EPA, and he currently holds a mid-career K24 award from NIDA.  He has also served as PI on more than 40 industry-funded clinical trials and is a consultant to a number of pharmaceutical companies in the area of ADHD clinical psychopharmacology.  He has served as a standing member of the Child Psychopathology and Developmental Disabilities study section and also served as an ad-hoc reviewer for 10 additional NIH study sections and 7 international granting agencies. He is an Associate Editor for the Journal of Attention Disorders and has reviewed for more than 50 different peer-reviewed journals. He is an elected member of the College on Problems of Drug Dependence and the American College of Neuropsychopharmacology. Dr. Kollins is a licensed clinical psychologist and maintains a practice through the ADHD Program’s outpatient clinic. His research interests are in the areas of psychopharmacology and the intersection of ADHD and substance abuse, particularly cigarette smoking.

Murphy

Susan Kay Murphy

Associate Professor in Obstetrics and Gynecology

Dr. Murphy is a tenured Associate Professor in the Department of Obstetrics and Gynecology and serves as Chief of the Division of Reproductive Sciences. As a molecular biologist with training in human epigenetics, her research interests are largely centered around the role of epigenetic modifications in health and disease. 

Dr. Murphy has ongoing projects on gynecologic malignancies, including approaches to eradicate ovarian cancer cells that survive chemotherapy and later give rise to recurrent disease. Dr. Murphy is actively involved in many collaborative projects relating to the Developmental Origins of Health and Disease (DOHaD).

Her lab is currently working on preconception environmental exposures in males, particularly on the impact of cannabis on the sperm epigenome and the potential heritability of these effects. They are also studying the epigenetic and health effects of in utero exposures, with primary focus on children from the Newborn Epigenetics STudy (NEST), a pregnancy cohort she co-founded who were recruited from central North Carolina between 2005 and 2011. Dr. Murphy and her colleagues continue to follow NEST children to determine relationships between prenatal exposures and later health outcomes.


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