Citation

Agrawal A, Lynskey MT. Addiction 2009; 104(4): 518-532.

Copyright

(Copyright © 2009, John Wiley and Sons)

DOI

10.1111/j.1360-0443.2009.02504.x

PMID

unavailable

Abstract

Aim  Twin studies have shown that cannabis use disorders (abuse/dependence) are highly heritable. This review aims to: (i) review existing linkage studies of cannabis use disorders and (ii) review gene association studies, to identify potential candidate genes, including those that have been tested for composite substance use disorders and (iii) to highlight challenges in the genomic study of cannabis use disorders.

Methods  Peer‐reviewed linkage and candidate gene association studies are reviewed.

Results  Four linkage studies are reviewed: results from these have homed in on regions on chromosomes 1, 3, 4, 9, 14, 17 and 18, which harbor candidates of predicted biological relevance, such as monoglyceride lipase (MGLL) on chromosome 3, but also novel genes, including ELTD1[epidermal growth factor (EGF), latrophilin and seven transmembrane domain containing 1] on chromosome 1. Gene association studies are presented for (a) genes posited to have specific influences on cannabis use disorders: CNR1, CB2, FAAH, MGLL, TRPV1 and GPR55 and (b) genes from various neurotransmitter systems that are likely to exert a non‐specific influence on risk of cannabis use disorders, e.g. GABRA2, DRD2 and OPRM1.

Conclusions  There are challenges associated with (i) understanding biological complexity underlying cannabis use disorders (including the need to study gene–gene and gene–environment interactions), (ii) using diagnostic versus quantitative phenotypes, (iii) delineating which stage of cannabis involvement (e.g. use versus misuse) genes influence and (iv) problems of sample ascertainment.