“A Large-Scale Genome-Wide Association Study Meta-Analysis of Cannabis Use Disorder”, Emma C. Johnson, Ditte Demontis, Thorgeir E. Thorgeirsson, Raymond K. Walters, Renato Polimanti, Alexander S. Hatoum, Sandra Sanchez-Roige, Sarah E. Paul, Frank R. Wendt, Toni-Kim Clarke, Dongbing Lai, Gunnar W. Reginsson, Hang Zhou, June He, David A. A. Baranger, Daniel F. Gudbjartsson, Robbee Wedow, Daniel E. Adkins, Amy E. Adkins, Jeffry Alexander, Silviu-Alin Bacanu, Tim B. Bigdeli, Joseph Boden, Sandra A. Brown, Kathleen K. Bucholz, Jonas Bybjerg-Grauholm, Robin P. Corley, Louisa Degenhardt, Danielle M. Dick, Benjamin W. Domingue, Louis Fox, Alison M. Goate, Scott D. Gordon, Laura M. Hack, Dana B. Hancock, Sarah M. Hartz, Ian B. Hickie, David Hougaard, Kenneth Krauter, Penelope A. Lind, Jeanette N. McClintick, Matthew B. McQueen, Jacquelyn L. Meyers, Grant W. Montgomery, Ole Mors, Preben Bo Mortensen, Merete Nordentoft, John F. Pearson, Roseann E. Peterson, Maureen D. Reynolds, John P. Rice, Valgerdur Runarsdottir, Nancy L. Saccone, Richard Sherva, Judy L. Silberg, Ralph E. Tarter, Thorarinn Tyrfingsson, Tamara L. Wall, Bradley T. Webb, Thomas Werge, Leah Wetherill, Margaret J. Wright, Stephanie Zellers, Mark J. Adams, Laura J. Bierut, Jason D. Boardman, William E. Copeland, Lindsay A. Farrer, Tatiana M. Foroud, Nathan A. Gillespie, Richard A. Grucza, Kathleen Mullan Harris, Andrew C. Heath, Victor Hesselbrock, John K. Hewitt, Christian J. Hopfer, John Horwood, William Iacono, Eric O. Johnson, Kenneth S. Kendler, Martin A. Kennedy, Henry R. Kranzler, Pamela A. F. Madden, Hermine H. Maes, Brion S. Maher, Nicholas G. Martin, Matthew McGue, Andrew M. McIntosh, Sarah E. Medland, Elliot C. Nelson, Bernice Porjesz, Brien P. Riley, Michael C. Stallings, Michael M. Vanyukov, Scott Vrieze, Lea K. Davis, Ryan Bogdan, Joel Gelernter, Howard J. Edenberg, Kari Stefansson, Anders Børglum, Arpana Agrawal2020 (genetic correlation, marijuana, ADHD, depression, SCZ)⁠:

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder.

Method: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesized associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations.

Findings: We identified two genome-wide statistically-significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p = 1·84 × 10⁻⁹) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p = 6·46 × 10⁻⁹).

Cannabis use disorder and cannabis use were genetically correlated (r_g 0·50, p = 1·50 × 10⁻²¹), but they showed statistically-significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia.

Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder.