DSM-5 cannabis use disorder: a phenotypic and genomic perspective.
- Authors
- Agrawal, Arpana; Lynskey, Michael T; Bucholz, Kathleen K; Kapoor, Manav; Almasy, Laura; Dick, Danielle M; Edenberg, Howard J; Foroud, Tatiana; Goate, Alison; Hancock, Dana B; Hartz, Sarah; Johnson, Eric O; Hesselbrock, Victor; Kramer, John R; Kuperman, Samuel; Nurnberger, John I; Schuckit, Marc; Bierut, Laura J
- Year
- 2014
- Journal
- Drug and alcohol dependence
- PMID
- 24315570
- DOI
- 10.1016/j.drugalcdep.2013.11.008
- PMCID
- PMC3943464
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.
Regional association plot of chromosome 17 results from the European-American subsample. SNP with lowest p-value (diamond-shape, in purple).
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