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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.

journal_name

Drug Alcohol Depend

journal_title

Drug and alcohol dependence

authors

Agrawal A,Lynskey MT,Bucholz KK,Kapoor M,Almasy L,Dick DM,Edenberg HJ,Foroud T,Goate A,Hancock DB,Hartz S,Johnson EO,Hesselbrock V,Kramer JR,Kuperman S,Nurnberger JI Jr,Schuckit M,Bierut LJ

doi

10.1016/j.drugalcdep.2013.11.008

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

362-369

eissn

0376-8716

issn

1879-0046

pii

S0376-8716(13)00476-6

journal_volume

134

pub_type

杂志文章

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