Format

Send to

Choose Destination
Drug Alcohol Depend. 2014 Jan 1;134:362-369. doi: 10.1016/j.drugalcdep.2013.11.008. Epub 2013 Nov 16.

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

Author information

1
Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA. Electronic address: arpana@wustl.edu.
2
Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA; King's College, Institute of Psychiatry, London, UK.
3
Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, USA.
4
Texas Biomedical Research Institute, San Antonio, TX, USA.
5
Virginia Commonwealth University, Virginia Institute of Psychiatric and Behavioral Genetics, VA, USA.
6
Indiana University School of Medicine, Indianapolis, IN, USA.
7
RTI International, Behavioral and Health Epidemiology Program, Research Triangle Park, NC, USA.
8
University of Connecticut, Department of Psychiatry, Farmington, CT, USA.
9
University of Iowa School of Medicine, Department of Psychiatry, Iowa City, IA, USA.
10
University of Iowa Hospitals, Division of Child Psychiatry, Iowa City, IA, USA.
11
University of California at San Diego, Department of Psychiatry, San Diego, CA, USA.

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.

KEYWORDS:

Association; Cannabis; DSM-5; GWAS; Genetics; Heritability

PMID:
24315570
PMCID:
PMC3943464
DOI:
10.1016/j.drugalcdep.2013.11.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center