title: DSM-5 cannabis use disorder: a phenotypic and genomic perspective.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA. Electronic address: arpana@wustl.edu.
authors: Arpana
authors: A
authors: Agrawal
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA; King's College, Institute of Psychiatry, London, UK.
authors: Michael T
authors: MT
authors: Lynskey
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors: Kathleen K
authors: KK
authors: Bucholz
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors: Manav
authors: M
authors: Kapoor
authors: Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Laura
authors: L
authors: Almasy
authors: Virginia Commonwealth University, Virginia Institute of Psychiatric and Behavioral Genetics, VA, USA.
authors: Danielle M
authors: DM
authors: Dick
authors: Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Howard J
authors: HJ
authors: Edenberg
authors: Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Tatiana
authors: T
authors: Foroud
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors: Alison
authors: A
authors: Goate
authors: RTI International, Behavioral and Health Epidemiology Program, Research Triangle Park, NC, USA.
authors: Dana B
authors: DB
authors: Hancock
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors: Sarah
authors: S
authors: Hartz
authors: RTI International, Behavioral and Health Epidemiology Program, Research Triangle Park, NC, USA.
authors: Eric O
authors: EO
authors: Johnson
authors: University of Connecticut, Department of Psychiatry, Farmington, CT, USA.
authors: Victor
authors: V
authors: Hesselbrock
authors: University of Iowa School of Medicine, Department of Psychiatry, Iowa City, IA, USA.
authors: John R
authors: JR
authors: Kramer
authors: University of Iowa Hospitals, Division of Child Psychiatry, Iowa City, IA, USA.
authors: Samuel
authors: S
authors: Kuperman
authors: Indiana University School of Medicine, Indianapolis, IN, USA.
authors: John I
authors: JI
authors: Nurnberger
authors: University of California at San Diego, Department of Psychiatry, San Diego, CA, USA.
authors: Marc
authors: M
authors: Schuckit
authors: Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
authors: Laura J
authors: LJ
authors: Bierut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
keywords: Association; Cannabis; DSM-5; GWAS; Genetics; Heritability