Grant: Project Grant

Accidental and fatal opioid overdose is a serious national concern, as it is responsible for the vast majority of all opioid-related deaths. While social and demographic risk factors for opioid overdose are well known, there are currently no validated biological risk factors to address the opioid crisis. In this project, we aim to use genomic-based approaches to identify individuals at a greater risk for accidental and fatal opioid overdose. For this purpose, we will collect 800 cases of accidental opioid-related deaths through our collaboration with the Office of the Chief Coroner of Ontario and the Ontario Forensic Pathology Service. First, we will examine the role of non-genetic risk factors such as sex, age and use of co-intoxicants. Then, we will investigate common genetic variation related to opioid metabolizing enzymes and the mechanism of action (i.e., receptor binding) in accidental opioid deaths. We will compare the frequencies of those variants to a matched population with chronic opioid use disorder but without escalating toward fatal overdosing. Lastly, we will investigate whether the combination of non-genetic and genetic risk scores is associated with accidental opioid-related deaths. Overall, we expect that our analyses will lead to a deeper understanding of an individual's genetic susceptibility to opioid overdose. We believe that by understanding the risk factors contributing to opioid overdose, we will set the stage to develop personalized prevention and treatment strategies, designed to reduce both overdose and economic burden to the healthcare system.