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Multi-ancestry Genome-wide Association Study of Cannabis Use Disorder Yields Insight Into Disease Biology and Public Health Implications

November 20, 2023

In a landmark research study, scientists have unveiled the results of a comprehensive genome-wide association study (GWAS), published in Nature Genetics, shedding new light on the genetic factors underlying cannabis use disorders (CanUD) and their potential link to lung cancer.

GWAS studies can locate genetic risk variants anywhere in the genome. This groundbreaking study, led by a team of researchers and from Yale University and the U.S. Department of Veterans Affairs (USVA), has identified 22 genetic variations associated with CanUD and potential causal consequences for lung cancer.

Cannabis use is prevalent worldwide and with trends toward legalization, it is increasing with growing numbers of individuals experiencing cannabis use disorders.

Understanding the genetic basis of CanUD is critical for understanding the biology that places some people at higher risk of dependence than others, and for developing effective prevention and treatment strategies.

Additionally, the potential link between cannabis use and lung cancer has been a subject of scientific curiosity and concern. The study employed data from the Million Veteran Program, a major USVA initiative, and also data from many other studies in a meta-analysis.

Key findings from the study include:

  • Identification of 22 Genetic Risk Regions: The study identified hundreds of risk variants located in 22 chromosomal locations significantly associated with cannabis use disorder. Studying these variants provided new insights into the genetic basis of CanUD and may inform future research and interventions.
  • Potential Causal Consequences for Lung Cancer: The study also revealed intriguing evidence suggesting potential causal consequences between cannabis use and lung cancer. While further research is required to establish a definitive link, these findings raise important questions about the health implications of cannabis use.
  • Cannabis Use, Dependence, and Mental Health: Another significant discovery from the study is the distinct patterns observed in the relationship between CanUD versus cannabis use (without dependence) with mental health traits. This finding highlights the complexity of these disorders and suggests that they may have unique genetic underpinnings and risk factors.

Daniel F. Levey, PhD, assistant professor of psychiatry, a USVA Career Award Investigator, and first author of the study, remarked, "Our research represents a significant step forward in our understanding of genetic architecture underlying cannabis use disorders, their relationship to psychopathology, and their potential health consequences. For example, we were able to compare self-reported cannabis use to diagnosed cannabis use disorder. We found diagnosed cannabis use disorders are positively associated with symptoms of post-traumatic stress disorder, while cannabis use was not. Schizophrenia on the other hand was found to be positively associated with both cannabis use and cannabis use disorder. "

The research team utilized state-of-the-art genomic techniques and analyzed data from a diverse population, ensuring the robustness and applicability of their findings. The study's publication underscores the scientific community's recognition of its significance.

According Joel Gelernter, MD, Foundations Fund Professor of Psychiatry at Yale School of Medicine, a VA Connecticut Healthcare System scientist, and senior author of the study, ”This study is a step forward in helping us to understand the biology of cannabis use disorder, and provides us with better tools to work out how this disorder relates genetically and biologically to other disorders. This information may help in developing pharmacotherapy for cannabis use disorder. Attaining a genomewide view of cannabis use disorder risk is also a step towards – eventually -- being able to personalize risk prediction and treatment.”

This discovery could mark a pivotal moment in the field of genetics and cannabis research, offering valuable insights into the interplay between genetics, cannabis use, psychopathology, and potential public health outcomes.

Submitted by Christopher Gardner on November 20, 2023