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A Large-Scale Genome-Wide Association Study Meta-Analysis of Cannabis use Disorder

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, et al. (2020). A Large-Scale Genome-Wide Association Study Meta-Analysis of Cannabis use Disorder. Lancet Psychiatry, 7(12), 1032-1045. PMCID: PMC7674631

Abstract

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.
METHODS: 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 hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations.
FINDINGS: We identified two genome-wide 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 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.

URL

http://dx.doi.org/10.1016/s2215-0366(20)30339-4

Reference Type

Journal Article

Year Published

2020

Journal Title

Lancet Psychiatry

Author(s)

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 M.
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 S.
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
Psychiatric Genomics Consortium Substance Use Disorders Workgroup,
Davis, Lea K.
Bogdan, Ryan
Gelernter, Joel E.
Edenberg, Howard J.
Stefansson, Kari
Børglum, Anders D.
Agrawal, Arpana

PMCID

PMC7674631

Data Set/Study

Psychiatric Genomics Consortium Substance Use Disorders working group
deCODE
iPSYCH

Continent/Country

Nonspecific