DSM-5 cannabis use disorder: a phenotypic and genomic perspective

Arpana Agrawal; Michael T Lynskey; Kathleen K Bucholz; Manav Kapoor; Laura Almasy; Danielle M Dick; Howard J Edenberg; Tatiana Foroud; Alison Goate; Dana B Hancock; Sarah Hartz; Eric O Johnson; Victor Hesselbrock; John R Kramer; Samuel Kuperman; John I Nurnberger Jr; Marc Schuckit; Laura J Bierut

doi:10.1016/j.drugalcdep.2013.11.008

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DSM-5 cannabis use disorder: a phenotypic and genomic perspective

Journal article

Open access

Peer reviewed

DSM-5 cannabis use disorder: a phenotypic and genomic perspective

Arpana Agrawal, Michael T Lynskey, Kathleen K Bucholz, Manav Kapoor, Laura Almasy, Danielle M Dick, Howard J Edenberg, Tatiana Foroud, Alison Goate, Dana B Hancock, …

Drug and alcohol dependence, Vol.134(1), pp.362-369

01/01/2014

DOI: 10.1016/j.drugalcdep.2013.11.008

PMCID: PMC3943464

PMID: 24315570

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Abstract

We explore the factor structure of DSM-5 cannabis use disorders, examine its prevalence across European- and African-American respondents as well as its genetic underpinnings, utilizing data from a genome-wide study of single nucleotide polymorphisms (SNPs). We also estimate the heritability of DSM-5 cannabis use disorders explained by these common SNPs. Data on 3053 subjects reporting a lifetime history of cannabis use were utilized. Exploratory and confirmatory factor analyses were conducted to create a factor score, which was used in a genome-wide association analysis. p-values from the single SNP analysis were examined for evidence of gene-based association. The aggregate effect of all SNPs was also estimated using Genome-Wide Complex Traits Analysis. The unidimensionality of DSM-5 cannabis use disorder criteria was demonstrated. Comparing DSM-IV to DSM-5, a decrease in prevalence of cannabis use disorders was only noted in European-American respondents and was exceedingly modest. For the DSM-5 cannabis use disorders factor score, no SNP surpassed the genome-wide significance testing threshold. However, in the European-American subsample, gene-based association testing resulted in significant associations in 3 genes (C17orf58, BPTF and PPM1D) on chromosome 17q24. In aggregate, 21% of the variance in DSM-5 cannabis use disorders was explained by the genome-wide SNPs; however, this estimate was not statistically significant. DSM-5 cannabis use disorder represents a unidimensional construct, the prevalence of which is only modestly elevated above the DSM-IV version. Considerably larger sample sizes will be required to identify individual SNPs associated with cannabis use disorders and unequivocally establish its polygenic underpinnings.

Phenotype

Diagnostic and Statistical Manual of Mental Disorders

Humans

Middle Aged

Genotype

Male

Young Adult

Marijuana Abuse - diagnosis

Adolescent

Adult

Female

Aged

Genome-Wide Association Study - methods

Marijuana Abuse - genetics

Details

Title: Subtitle: DSM-5 cannabis use disorder: a phenotypic and genomic perspective
Creators: Arpana Agrawal - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA. Electronic address: arpana@wustl.edu
Michael T Lynskey - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA; King's College, Institute of Psychiatry, London, UK
Kathleen K Bucholz - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA
Manav Kapoor - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA
Laura Almasy - Texas Biomedical Research Institute, San Antonio, TX, USA
Danielle M Dick - Virginia Commonwealth University, Virginia Institute of Psychiatric and Behavioral Genetics, VA, USA
Howard J Edenberg - Indiana University School of Medicine, Indianapolis, IN, USA
Tatiana Foroud - Indiana University School of Medicine, Indianapolis, IN, USA
Alison Goate - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA
Dana B Hancock - RTI International, Behavioral and Health Epidemiology Program, Research Triangle Park, NC, USA
Sarah Hartz - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA
Eric O Johnson - RTI International, Behavioral and Health Epidemiology Program, Research Triangle Park, NC, USA
Victor Hesselbrock - University of Connecticut, Department of Psychiatry, Farmington, CT, USA
John R Kramer - University of Iowa School of Medicine, Department of Psychiatry, Iowa City, IA, USA
Samuel Kuperman - University of Iowa Hospitals, Division of Child Psychiatry, Iowa City, IA, USA
John I Nurnberger Jr - Indiana University School of Medicine, Indianapolis, IN, USA
Marc Schuckit - University of California at San Diego, Department of Psychiatry, San Diego, CA, USA
Laura J Bierut - Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA
Resource Type: Journal article
Publication Details: Drug and alcohol dependence, Vol.134(1), pp.362-369
DOI: 10.1016/j.drugalcdep.2013.11.008
PMID: 24315570
PMCID: PMC3943464
NLM abbreviation: Drug Alcohol Depend
ISSN: 0376-8716
eISSN: 1879-0046
Publisher: Ireland
Grant note: U01 HG004422 / NHGRI NIH HHS U01HG004438 / NHGRI NIH HHS R01 DA019963 / NIDA NIH HHS U01 HG004446 / NHGRI NIH HHS U10 AA008401 / NIAAA NIH HHS K08 DA032680 / NIDA NIH HHS K02 DA032573 / NIDA NIH HHS U01 HG004438 / NHGRI NIH HHS R01 DA013423 / NIDA NIH HHS UL1 TR000448 / NCATS NIH HHS HHSN268200782096C / NHGRI NIH HHS R01 DA023668 / NIDA NIH HHS UL1 TR001108 / NCATS NIH HHS HHSN268200782096C / NHLBI NIH HHS K02 AA018755 / NIAAA NIH HHS K02DA032573 / NIDA NIH HHS R01DA23668 / NIDA NIH HHS P01 CA089392 / NCI NIH HHS
Language: English
Date published: 01/01/2014
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003948902771

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