Link Between Genetic Variation, Lifetime Cannabis Use Found

A recent meta-analysis of genome-wide association study (GWAS) data of more than 32,000 individuals implicates 4 genes in lifetime cannabis use, according a report published in Translational Psychiatry. Multiple common genetic variants, or single nucleotide polymorphisms (SNPs), explained between 13% and 20% of the risk of lifetime cannabis use.¹

Cannabis-use disorder (CUD) is currently the most widely reported illegal substance use disorder, and approximately 30% of users exhibit signs of marijuana abuse or dependence.² Marijuana use is associated with development of various neuropsychiatric conditions such as schizophrenia, anxiety, and depression.¹

Human genetic studies reveal a heritability of lifetime cannabis use of approximately 40% to 48%, whereas environmental factors account for about 25% to 39% of the risk, depending on gender. No studies to date were successful at identifying any significant SNPs, most likely because the success of genome-wide experiments in detecting causal genes in complex neuropsychiatric disorders relies on a sufficiently large sample size. Also, multiple SNPs are hypothesized to work together to influence risk of disease, as individual SNPs exert a relatively small effect on overall risk.¹

In the present study, no genome-wide significant associations between individual SNPs and lifetime cannabis use were observed. However, 4 genes (NCAM1, CADM2, SCOC, and KCNT2) were associated with lifetime cannabis use.¹

Individual SNPs that are associated with substantial risk for lifetime cannabis use are not restricted to this disorder, but are shared among many conditions and may confer risk for other psychiatric and substance use disorders. “Our results indicate a very high overlap (r=0.83) between our measure of lifetime cannabis use and lifetime cigarette use when based on the SNP panel,” the investigators affiliated with the International Cannabis Consortium noted.

Previous studies have implicated NCAM1 in nicotine dependence and CADM2 was associated with autism disorders, whereas “suggestive association for SNPs near KCNT2 has previously been found for cocaine dependence and … heavy opioid use,” they wrote in the publication.

Although individual SNPs that increase the risk of lifetime cannabis use exert a relatively small effect and have pleiotropic biological effects, “we have identified 4 genes significantly associated with cannabis use, which are candidates for follow-up functional studies,” the authors concluded.

References

1. Stringer S, Minica CC, Verweij KJ, et al. Genome-wide association study of lifetime cannabis use based on a large met-analytic sample of 32 330 subjects from the International Cannabis Consortium. Transl Psychiatry. 2016;6:e769.

2. Hasin DS, Saha TD, Kerridge BT, et al. Prevalence of marijuana use disorders in the United States between 2001-2002 and 2012-2013. JAMA Psychiatry. 2015;72:1235-1242.