Arpana Agrawal1, Michael T Lynskey. 1. Washington University School of Medicine, Department of Psychiatry, St Louis, MO 63110, USA. arpana@wustl.edu
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.
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.
Authors: Arpana Agrawal; Howard J Edenberg; Tatiana Foroud; Laura J Bierut; Gerald Dunne; Anthony L Hinrichs; John I Nurnberger; Raymond Crowe; Samuel Kuperman; Marc A Schuckit; Henri Begleiter; Bernice Porjesz; Danielle M Dick Journal: Behav Genet Date: 2006-09 Impact factor: 2.805
Authors: M T Lynskey; A C Heath; E C Nelson; K K Bucholz; P A F Madden; W S Slutske; D J Statham; N G Martin Journal: Psychol Med Date: 2002-02 Impact factor: 7.723
Authors: Arpana Agrawal; Leah Wetherill; Danielle M Dick; Xiaoling Xuei; Anthony Hinrichs; Victor Hesselbrock; John Kramer; John I Nurnberger; Marc Schuckit; Laura J Bierut; Howard J Edenberg; Tatiana Foroud Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2009-07-05 Impact factor: 3.568
Authors: Nathan A Gillespie; Michael C Neale; Carol A Prescott; Steven H Aggen; Kenneth S Kendler Journal: Addiction Date: 2007-06 Impact factor: 6.526
Authors: Kent E Hutchison; Heather Haughey; Michelle Niculescu; Joe Schacht; Alan Kaiser; Jerry Stitzel; William J Horton; Francesca Filbey Journal: Arch Gen Psychiatry Date: 2008-07
Authors: Rheal A Towner; Randy L Jensen; Howard Colman; Brian Vaillant; Nataliya Smith; Rebba Casteel; Debra Saunders; David L Gillespie; Robert Silasi-Mansat; Florea Lupu; Cory B Giles; Jonathan D Wren Journal: Neurosurgery Date: 2013-01 Impact factor: 4.654
Authors: Francesca M Filbey; Joseph P Schacht; Ursula S Myers; Robert S Chavez; Kent E Hutchison Journal: Neuropsychopharmacology Date: 2009-12-09 Impact factor: 7.853
Authors: Caitlin E Carey; Arpana Agrawal; Bo Zhang; Emily D Conley; Louisa Degenhardt; Andrew C Heath; Daofeng Li; Michael T Lynskey; Nicholas G Martin; Grant W Montgomery; Ting Wang; Laura J Bierut; Ahmad R Hariri; Elliot C Nelson; Ryan Bogdan Journal: J Abnorm Psychol Date: 2015-11