Cannabis use disorder has genetic association with multiple adverse psychiatric outcomes
Cannabis use disorder appeared to have a genetic association with multiple adverse psychiatric outcomes, according to results of a genome-wide association study meta-analysis published in The Lancet Psychiatry.
“A [genome-wide association study] of lifetime cannabis use identified eight genome-wide significant loci and 35 significant genes,” Emma C. Johnson, PhD, of the department of psychiatry at Washington University School of Medicine in Missouri, and colleagues wrote. “Twin studies suggest high genetic correlations between early stages of cannabis experimentation and later cannabis use disorder. However, casual cannabis use is affected by a variety of socioenvironmental influences and age-period-cohort effects, whereas progression to cannabis use disorder is related to other psychopathologies.”
Johnson and colleagues aimed to evaluate the genomic liability for cannabis use disorder, as well as to assess whether the genetic factors related to cannabis use and cannabis use disorder diverge with respect to brain and behavioral measures. They analyzed 363,116 control samples and 20,916 case samples included in the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH and deCODE, and compared cannabis use disorder cases with controls. Further, they used linkage disequilibrium score regression to examine the genetic link between cannabis use disorder and 22 traits chosen because of prior study results that showed phenotypic correlations or hypothesized associations.
Results suggested a novel chromosome 7 locus and the previously identified chromosome 8 locus as two genome-wide significant loci. The researchers reported that cannabis use and cannabis use disorder had a genetic correlation; however, the exhibited significantly different genetic relationships to 12 of the 22 tested traits, which suggested at least partially different genetic underpinnings between the two. They also observed a positive genetic correlation between cannabis use disorder and other psychopathology, such as schizophrenia, ADHD and major depression.
“Our findings provide further evidence that cannabis use disorder is a serious, psychiatric illness with genetic and neurobiological influences that diverge at least partially from cannabis use,” Johnson and colleagues wrote. “From a public health perspective, the recognition that cannabis use disorder is a serious form of psychopathology should spur efforts to identify and aid at-risk individuals in the face of escalating cannabis use worldwide, especially among adolescents.”
In a related editorial, Lindsey A. Hines, PhD, of Population Health Science at Bristol Medical School in the U.K., and colleagues highlighted the future opportunities for research that these findings provide.
“There is now increasing scope to explore the complex pathways between stages of substance use (e.g., from initiation to frequency of use and dependence), and the use of multiple substances (e.g., the common use of cannabis and tobacco, which makes their epidemiological dissection challenging),” they wrote. “To support strong causal inference, and therefore robust public health policies, findings from Mendelian randomization should be considered alongside those from other methodological approaches that also aim to understand the harms of cannabis use. This approach is known as triangulation. Understanding these pathways will be crucial if evidence-based public health policies are to be implemented.”