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.
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.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 362-369 |
| Number of pages | 8 |
| Journal | Drug and alcohol dependence |
| Volume | 134 |
| Issue number | N/A |
| DOIs | |
| Publication status | Published - 1 Jan 2014 |