Genetic basis of cannabis use: a systematic review

Alannah Hillmer; Caroul Chawar; Stephanie Sanger; Alessia D'Elia; Mehreen Butt; Raveena Kapoor; Flavio Kapczinski; Lehana Thabane; Zainab Samaan

doi:10.1186/s12920-021-01035-5

Genetic basis of cannabis use: a systematic review

BMC Med Genomics. 2021 Aug 12;14(1):203. doi: 10.1186/s12920-021-01035-5.

Authors

Alannah Hillmer¹, Caroul Chawar¹, Stephanie Sanger², Alessia D'Elia¹, Mehreen Butt³, Raveena Kapoor⁴, Flavio Kapczinski¹, Lehana Thabane⁵, Zainab Samaan⁶

Affiliations

¹ Neuroscience Graduate Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th St., Hamilton, ON, L8N 3K7, Canada.
² Health Science Library, McMaster University, 1280 Main St. W., Hamilton, ON, L8S 4L8, Canada.
³ Integrated Science Program, McMaster University, 1280 Main St. W., Hamilton, ON, L8S 4L8, Canada.
⁴ Michael G. DeGroote School of Medicine, McMaster University, 1280 Main St. W., Hamilton, ON, L8S 4L8, Canada.
⁵ Department of Health Research Method, Evidence and Impact, 1280 Main St. W., Hamilton, ON, L8S 4L8, Canada.
⁶ Neuroscience Graduate Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 100 West 5th St., Hamilton, ON, L8N 3K7, Canada. samaanz@mcmaster.ca.

Abstract

Background: With 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.

Methods: This 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.

Results: Our 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.

Conclusion: This 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.

Keywords: Cannabis; Genetics; Genome-wide Association Study; Systematic review.

Publication types

Systematic Review

MeSH terms

Cannabis / adverse effects
Cannabis / genetics
Genetic Predisposition to Disease
Genome-Wide Association Study*
Humans
Marijuana Abuse / genetics
Marijuana Use / genetics

Grants and funding

PJT-156306/CIHR/Canada