A massive genetic analysis of over 384,000 people identified 22 genome regions linked to cannabis use disorder risk, with significant genetic overlap with other psychiatric conditions.
Genetics researchers, addiction scientists, and clinicians interested in the biological basis of cannabis use disorder.
22 genome-wide significant loci identified across 384,032 participants
What the researchers found
This GWAS meta-analysis identified 22 genome-wide significant loci associated with cannabis use disorder, with SNP-based heritability estimated at 11%. Strong genetic correlations were found with other substance use disorders, ADHD, major depression, and schizophrenia.
Why it matters
This is one of the largest genetic studies of cannabis use disorder ever conducted. It provides the clearest picture yet of the biological architecture of problematic cannabis use and its genetic connections to other psychiatric conditions.
The numbers in context
384,032 participants; 42,281 CUD cases; 22 genome-wide significant loci; SNP heritability of 11%; published in Lancet Psychiatry.
How the study worked
Genome-wide association study meta-analysis combining data from multiple cohorts totaling 384,032 participants of European ancestry, including 42,281 CUD cases.
What this study cannot tell us
Limited to European ancestry, reducing generalizability to other populations. Common genetic variants explain only a fraction of total heritability. Genetic associations do not imply simple causal mechanisms.
How to read the evidence
Strong: massive sample size, rigorous GWAS methodology, published in top-tier journal (Lancet Psychiatry).
When this study was published
Published 2023.
The bigger picture
The strong genetic overlap between cannabis use disorder and conditions like ADHD, depression, and schizophrenia suggests shared biological pathways. This could eventually lead to better screening tools and targeted interventions for those at highest genetic risk.
Questions still open
- Will these findings replicate in diverse ancestry groups? Can polygenic risk scores eventually be used clinically to identify high-risk individuals before problems develop?
Common questions
How heritable is cannabis use disorder?
Which psychiatric conditions share genetic risk with cannabis use disorder?
Read the original research
A large-scale genome-wide association study meta-analysis of cannabis use disorder.
The lancet. Psychiatry, 7(12), 1032-1045
Citation
Johnson, Emma C; Demontis, Ditte; Thorgeirsson, Thorgeir E; Walters, Raymond K; Polimanti, Renato; Hatoum, Alexander S; Sanchez-Roige, Sandra; Paul, Sarah E; Wendt, Frank R; Clarke, Toni-Kim; Lai, Dongbing; Reginsson, Gunnar W; Zhou, Hang; He, June; Baranger, David A A; Gudbjartsson, Daniel F; Wedow, Robbee; Adkins, Daniel E; Adkins, Amy E; Alexander, Jeffry; Bacanu, Silviu-Alin; Bigdeli, Tim B; Boden, Joseph; Brown, Sandra A; Bucholz, Kathleen K; Bybjerg-Grauholm, Jonas; Corley, Robin P; Degenhardt, Louisa; Dick, Danielle M; Domingue, Benjamin W; Fox, Louis; Goate, Alison M; Gordon, Scott D; Hack, Laura M; Hancock, Dana B; Hartz, Sarah M; Hickie, Ian B; Hougaard, David M; Krauter, Kenneth; Lind, Penelope A; McClintick, Jeanette N; McQueen, Matthew B; Meyers, Jacquelyn L; Montgomery, Grant W; Mors, Ole; Mortensen, Preben B; Nordentoft, Merete; Pearson, John F; Peterson, Roseann E; Reynolds, Maureen D; Rice, John P; Runarsdottir, Valgerdur; Saccone, Nancy L; Sherva, Richard; Silberg, Judy L; Tarter, Ralph E; Tyrfingsson, Thorarinn; Wall, Tamara L; Webb, Bradley T; Werge, Thomas; Wetherill, Leah; Wright, Margaret J; Zellers, Stephanie; Adams, Mark J; Bierut, Laura J; Boardman, Jason D; Copeland, William E; Farrer, Lindsay A; Foroud, Tatiana M; Gillespie, Nathan A; Grucza, Richard A; Harris, Kathleen Mullan; Heath, Andrew C; Hesselbrock, Victor; Hewitt, John K; Hopfer, Christian J; Horwood, John; Iacono, William G; Johnson, Eric O; Kendler, Kenneth S; Kennedy, Martin A; Kranzler, Henry R; Madden, Pamela A F; Maes, Hermine H; Maher, Brion S; Martin, Nicholas G; McGue, Matthew; McIntosh, Andrew M; Medland, Sarah E; Nelson, Elliot C; Porjesz, Bernice; Riley, Brien P; Stallings, Michael C; Vanyukov, Michael M; Vrieze, Scott; Davis, Lea K; Bogdan, Ryan; Gelernter, Joel; Edenberg, Howard J; Stefansson, Kari; Børglum, Anders D; Agrawal, Arpana. (2020). A large-scale genome-wide association study meta-analysis of cannabis use disorder.. The lancet. Psychiatry, 7(12), 1032-1045. https://doi.org/10.1016/S2215-0366(20)30339-4
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