Candidate genes for cannabis use disorders: Findings, challenges and directions

Arpana Agrawal, Michael T. Lynskey

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.

Original languageEnglish
Pages (from-to)518-532
Number of pages15
JournalAddiction
Volume104
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • Association
  • CNR1
  • Cannabis
  • FAAH
  • Genes
  • Linkage

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