Dissecting the shared origins of schizophrenia and chronic cannabis use: A genomic investigation
Aperçu du projet
Regular cannabis use is indisputably linked to schizophrenia. However, the causal nature and direction of this link is contentious and the biological mechanisms underpinning their relationship are poorly understood. Regular cannabis use is on the rise in Canada, so elucidating this relationship is timely and important. Genome-wide association studies (GWASs), by pinpointing the genes and biological mechanisms that confer disorder risk, can provide new insight into the origins of schizophrenia and cannabis use, and thereby facilitate interventions. However, current GWASs do not account for comorbidity between schizophrenia and cannabis use, which can confound results, mask the biology that is specific to each trait, and hinder treatment development. One solution is to repeat existing GWASs and screen for both cannabis use and schizophrenia in participants, an immense undertaking. Alternatively, modern genomic techniques can be applied to combine existing GWASs with statistical frameworks to make new GWASs that partition independent and joint genetic factors. I will employ this partitioning technique using the current best powered schizophrenia (N=161,405) and cannabis (N=1,017,920) GWASs, to which I have contributed. By coupling these new GWASs with functional annotation, I will uncover genes, pathways, and biological systems that can enable a deeper mechanistic understanding of schizophrenia and cannabis’ shared origins. GWASs can also be used to develop biomarkers (i.e., polygenic scores) that can be used for disorder prediction in individuals who are at-risk but do not yet have schizophrenia. I will leverage unique access to large medical datasets to examine the associations between partitioned schizophrenia and cannabis use biomarkers with thousands of other health outcomes, including schizophrenia diagnosis. This project will expand current knowledge on the biological relationship between schizophrenia and cannabis use, refine prediction biomarkers, and ultimately open new avenues for effective and targeted disorder management.
Chef d'équipe
Hayley Thorpe , University of Western Ontario
Partenaire et Donateurs
M. Wayne and J. Coleman Family Fund