Cannabis is the most commonly used illicit drug in the US, with 14% of Americans aged 12 or older reporting use during 2016 and 44% reporting lifetime use. Both acute (e.g., impaired motor function) and chronic health effects (e.g., dependence, cognitive function) of cannabis use have been reported. However, efforts to assess the scope of the adverse effects are hampered by under-reporting and the lack of available biomarkers which can reliably quantify cannabis usage patterns. Thus, there is a need to develop robust biomarkers of exposure to more accurately identify usage patterns in order to monitor those in treatment for adherence, fill-in missing cannabis use history, and/or predict health consequences. DNA methylation (DNAm) represents an excellent candidate for biomarker research, as it has the potential to differentiate acute vs. chronic exposure, timing of exposure, and cumulative exposure.

The overarching goal of the study is to identify the first reliable and useful blood-based DNAm biomarkers for cannabis use phenotypes. To achieve our goal, we propose to leverage the ALSPAC study, along with existing data from ~7 other cohorts to conduct the largest epigenome-wide (genome-wide DNAm) meta-analysis for any cannabis use phenotype to date (N~10,000 individuals across cohorts). From this, will identify and validate DNAm biomarkers of cannabis use representing general biomarkers (i.e., without regard to the etiology of the DNAm differences, possibly providing the greatest overall predictive ability), and those enriched for either exposure- or genetically-driven effects (i.e., DNAm as a mediator between genetic variants and cannabis use).