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. 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

Arpana Agrawal  1 , Michael T Lynskey  2 , Kathleen K Bucholz  3 , Manav Kapoor  3 , Laura Almasy  4 , Danielle M Dick  5 , Howard J Edenberg  6 , Tatiana Foroud  6 , Alison Goate  3 , Dana B Hancock  7 , Sarah Hartz  3 , Eric O Johnson  7 , Victor Hesselbrock  8 , John R Kramer  9 , Samuel Kuperman  10 , John I Nurnberger Jr  6 , Marc Schuckit  11 , Laura J Bierut  3
Affiliations

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

Arpana Agrawal et al. Drug Alcohol Depend. .

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.

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Figures

Figure 1
Figure 1
Regional association plot of chromosome 17 results from the European-American subsample. SNP with lowest p-value (diamond-shape, in purple).
See this image and copyright information in PMC

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