Abstract
BackgroundWith the increase in cannabis use rates, cannabis use disorder is being reported as one of the most common drug use disorders globally. Cannabis use has several known physical, psychological, and social adverse events, such as altered judgement, poor educational outcomes, and respiratory symptoms. The propensity for taking cannabis and the development of a cannabis use disorder may be genetically influenced for some individuals. Heritability estimates suggest a genetic basis for cannabis use, and several genome-wide association studies (GWASs) have identified possible regions of association, albeit with inconsistent findings. This systematic review aims to summarize the findings from GWASs investigating cannabis use and cannabis use disorder.MethodsThis systematic review incorporates articles that have performed a GWAS investigating cannabis use or cannabis use disorder. MEDLINE, Web of Science, EMBASE, CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotype and Phenotype were searched using a comprehensive search strategy. All studies were screened in duplicate, and the quality of evidence was assessed using the quality of genetic association studies (Q-Genie) tool. All studies underwent qualitative synthesis; however, quantitative analysis was not feasible.ResultsOur search identified 5984 articles. Six studies met our eligibility criteria and were included in this review. All six studies reported results that met our significance threshold of p ≤ 1.0 × 10–7. In total 96 genetic variants were identified. While meta-analysis was not possible, this review identified the following genes, ANKFN1, INTS7, PI4K2B, CSMD1, CST7, ACSS1, and SCN9A, to be associated with cannabis use. These regions were previously reported in different mental health conditions, however not in relation to cannabis use.ConclusionThis systematic review summarized GWAS findings within the field of cannabis research. While a meta-analysis was not possible, the summary of findings serves to inform future candidate gene studies and replication efforts.Systematic Review Registration PROSPERO CRD42020176016.
Highlights
Rationale Over the past two decades cannabis use and dependence are estimated to have increased, with cannabis use disorder (CUD) reported as one of the most common drug use disorders globally [1]
The threshold of significance of genetic variants reaching p ≤ 10–7 was set, as some Genome-wide association study (GWAS) results with this significance level have been shown to be replicable within the literature [21]
Agrawal et al [26] identified two SNPs associated with Diagnostic and Statistical Manual (DSM)-IV cannabis dependence within the ANKFN1 gene
Summary
Rationale Over the past two decades cannabis use and dependence are estimated to have increased, with cannabis use disorder (CUD) reported as one of the most common drug use disorders globally [1]. Repeated use of cannabis can have long lasting effects, including altered brain development, poor education outcome, cognitive impairment, diminished life satisfaction and achievement, poor professional and social achievements, symptoms of chronic bronchitis and increased risk of chronic psychotic disorders [3, 5]. With the increase in cannabis use rates, cannabis use disorder is being reported as one of the most common drug use disorders globally. Heritability estimates suggest a genetic basis for cannabis use, and several genome-wide association studies (GWASs) have identified possible regions of association, albeit with inconsistent findings. This systematic review aims to summarize the findings from GWASs investigating cannabis use and cannabis use disorder
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