期刊
DRUG AND ALCOHOL DEPENDENCE
卷 134, 期 -, 页码 362-369出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.drugalcdep.2013.11.008
关键词
Cannabis; DSM-5; GWAS; Association; Genetics; Heritability
资金
- Foundation for Alcohol Research/ABMRF
- NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]
- Gene Environment Association Studies (GENEVA) under GEI
- NIH GEI [U01HG004438]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH [HHSN268200782096C]
- [K02DA032573]
- [R01DA23668]
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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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