Largest genetic study of cannabis use disorder identifies 22 risk genes

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.

Johnson, Emma C et al.·The lancet. Psychiatry·2020·Strong EvidenceMeta-Analysis
RTHC-02633Meta AnalysisStrong Evidence2020RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Meta-Analysis
Evidence
Strong Evidence
Sample
N=384,032

What This Study 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.

Key Numbers

384,032 participants; 42,281 CUD cases; 22 genome-wide significant loci; SNP heritability of 11%; published in Lancet Psychiatry.

How They Did This

Genome-wide association study meta-analysis combining data from multiple cohorts totaling 384,032 participants of European ancestry, including 42,281 CUD cases.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?Will these findings replicate in diverse ancestry groups?
  • ?Can polygenic risk scores eventually be used clinically to identify high-risk individuals before problems develop?

Trust & Context

Key Stat:
22 genome-wide significant loci identified across 384,032 participants
Evidence Grade:
Strong: massive sample size, rigorous GWAS methodology, published in top-tier journal (Lancet Psychiatry).
Study Age:
Published 2023.
Original Title:
A large-scale genome-wide association study meta-analysis of cannabis use disorder.
Published In:
The lancet. Psychiatry, 7(12), 1032-1045 (2020)
Authors:
Johnson, Emma C(17), Demontis, Ditte(4), Thorgeirsson, Thorgeir E(2), 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
Database ID:
RTHC-02633

Evidence Hierarchy

Meta-Analysis / Systematic ReviewCombines many studies into one answer
This study
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal Study

Combines results from multiple studies to find an overall pattern.

What do these levels mean? →

Frequently Asked Questions

How heritable is cannabis use disorder?

This study estimated SNP-based heritability at about 11%, meaning common genetic variants account for roughly 11% of the variation in CUD risk. Total heritability from twin studies is estimated higher (50-70%).

Which psychiatric conditions share genetic risk with cannabis use disorder?

Significant genetic correlations were found with other substance use disorders, ADHD, major depressive disorder, and schizophrenia.

Read More on RethinkTHC

Cite This Study

RTHC-02633·https://rethinkthc.com/research/RTHC-02633

APA

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

MLA

Johnson, Emma C, et al. "A large-scale genome-wide association study meta-analysis of cannabis use disorder.." The lancet. Psychiatry, 2020. https://doi.org/10.1016/S2215-0366(20)30339-4

RethinkTHC

RethinkTHC Research Database. "A large-scale genome-wide association study meta-analysis of..." RTHC-02633. Retrieved from https://rethinkthc.com/research/johnson-2020-a-largescale-genomewide-association

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.