Journal article
A large-scale genome-wide association study meta-analysis of cannabis use disorder
The Lancet. Psychiatry, Vol.7(12), pp.1032-1045
12/2020
DOI: 10.1016/S2215-0366(20)30339-4
PMCID: PMC7674631
PMID: 33096046
Abstract
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.
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.
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
) 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
). Cannabis use disorder and cannabis use were genetically correlated (r
0·50, p=1·50 × 10
), 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.
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.
National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.
Details
- Title: Subtitle
- A large-scale genome-wide association study meta-analysis of cannabis use disorder
- Creators
- Emma C Johnson - Washington University in St. LouisDitte Demontis - Aarhus UniversityThorgeir E Thorgeirsson - CNSRaymond K Walters - Harvard UniversityRenato Polimanti - Yale UniversityAlexander S Hatoum - Washington University in St. LouisSandra Sanchez-Roige - University of California, San DiegoSarah E Paul - Washington University in St. LouisFrank R Wendt - Yale UniversityToni-Kim Clarke - University of EdinburghDongbing Lai - Indiana UniversityGunnar W Reginsson - CNSHang Zhou - Yale UniversityJune He - Washington University in St. LouisDavid A A Baranger - University of PittsburghDaniel F GudbjartssonRobbee Wedow - Harvard UniversityDaniel E Adkins - Virginia Commonwealth UniversityAmy E Adkins - Virginia Commonwealth UniversityJeffry Alexander - Virginia Commonwealth UniversitySilviu-Alin Bacanu - Virginia Commonwealth UniversityTim B Bigdeli - SUNY Downstate Medical CenterJoseph Boden - University of OtagoSandra A Brown - University of California, San DiegoKathleen K Bucholz - Washington University in St. LouisJonas Bybjerg-Grauholm - Statens Serum InstitutRobin P Corley - University of Colorado BoulderLouisa Degenhardt - National Drug and Alcohol Research CentreDanielle M Dick - Virginia Commonwealth UniversityBenjamin W Domingue - Stanford UniversityLouis Fox - Washington University in St. LouisAlison M Goate - Icahn School of Medicine at Mount SinaiScott D Gordon - QIMR Berghofer Medical Research InstituteLaura M Hack - Stanford UniversityDana B Hancock - Research Triangle Park FoundationSarah M Hartz - Washington University in St. LouisIan B Hickie - University of SydneyDavid M Hougaard - Statens Serum InstitutKenneth Krauter - University of Colorado BoulderPenelope A Lind - QIMR Berghofer Medical Research InstituteJeanette N McClintick - Indiana UniversityMatthew B McQueen - University of Colorado BoulderJacquelyn L Meyers - SUNY Downstate Medical CenterGrant W Montgomery - University of QueenslandOle Mors - Aarhus University HospitalPreben B Mortensen - Aarhus UniversityMerete Nordentoft - University of CopenhagenJohn F Pearson - University of OtagoRoseann E Peterson - Virginia Commonwealth UniversityMaureen D Reynolds - University of PittsburghJohn P Rice - Washington University in St. LouisValgerdur Runarsdottir - SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, IcelandNancy L Saccone - Washington University in St. LouisRichard Sherva - Boston UniversityJudy L Silberg - Virginia Commonwealth UniversityRalph E Tarter - University of PittsburghThorarinn Tyrfingsson - SAA-National Center of Addiction Medicine, Vogur Hospital, Reykjavik, IcelandTamara L Wall - University of California, San DiegoBradley T Webb - Virginia Commonwealth UniversityThomas Werge - Copenhagen University HospitalLeah Wetherill - Indiana UniversityMargaret J Wright - University of QueenslandStephanie Zellers - University of MinnesotaMark J Adams - University of EdinburghLaura J Bierut - Washington University in St. LouisJason D Boardman - University of Colorado BoulderWilliam E Copeland - University of Vermont Medical CenterLindsay A Farrer - Boston UniversityTatiana M Foroud - Indiana UniversityNathan A Gillespie - Virginia Commonwealth UniversityRichard A Grucza - Washington University in St. LouisKathleen Mullan Harris - University of North Carolina at Chapel HillAndrew C Heath - Washington University in St. LouisVictor Hesselbrock - University of ConnecticutJohn K Hewitt - University of Colorado BoulderChristian J Hopfer - University of Colorado DenverJohn Horwood - University of OtagoWilliam G Iacono - University of MinnesotaEric O Johnson - Research Triangle Park FoundationKenneth S Kendler - Virginia Commonwealth UniversityMartin A Kennedy - University of OtagoHenry R Kranzler - University of PennsylvaniaPamela A F Madden - Washington University in St. LouisHermine H Maes - Virginia Commonwealth UniversityBrion S Maher - Johns Hopkins UniversityNicholas G Martin - QIMR Berghofer Medical Research InstituteMatthew McGue - University of MinnesotaAndrew M McIntosh - University of EdinburghSarah E Medland - QIMR Berghofer Medical Research InstituteElliot C Nelson - Washington University in St. LouisBernice Porjesz - SUNY Downstate Medical CenterBrien P Riley - Virginia Commonwealth UniversityMichael C Stallings - University of Colorado BoulderMichael M Vanyukov - University of PittsburghScott Vrieze - University of MinnesotaLea K Davis - Vanderbilt University Medical CenterRyan Bogdan - Washington University in St. LouisJoel Gelernter - Yale UniversityHoward J Edenberg - Indiana UniversityKari Stefansson - RMIT UniversityAnders D Børglum - Aarhus UniversityArpana Agrawal - Washington University in St. LouisPsychiatric Genomics Consortium Substance Use Disorders Workgroup
- Contributors
- Samuel Kuperman (Contributor) - University of Iowa, Psychiatry
- Resource Type
- Journal article
- Publication Details
- The Lancet. Psychiatry, Vol.7(12), pp.1032-1045
- DOI
- 10.1016/S2215-0366(20)30339-4
- PMID
- 33096046
- PMCID
- PMC7674631
- ISSN
- 2215-0366
- eISSN
- 2215-0374
- Grant note
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- Language
- English
- Date published
- 12/2020
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293753002771
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