A large-scale genome-wide association study meta-analysis of cannabis use disorder

Emma Johnson; Jouke Hottenga; Lannie Ligthart; Hamdi Mbarek; Yuri Milaneschi; Dorret Boomsma; Arpana Agrawal; Psychiatric Genomics Consortium Substance Use Disorders Workgroup

doi:10.1016/S2215-0366(20)30339-4

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Emma Johnson
, Jouke Hottenga
, Lannie Ligthart
, Hamdi Mbarek
, Yuri Milaneschi
, Dorret Boomsma
, Arpana Agrawal
, Psychiatric Genomics Consortium Substance Use Disorders Workgroup

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Funding: 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.

Original language	English
Pages (from-to)	1032-1045
Number of pages	14
Journal	The Lancet Psychiatry
Volume	7
Issue number	12
Early online date	20 Oct 2020
DOIs	https://doi.org/10.1016/S2215-0366(20)30339-4
Publication status	Published - Dec 2020

Funding

The Psychiatric Genomics Consortium's Substance Use Disorders working group is supported by MH109532 with funding from the National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA). We gratefully acknowledge previous support from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and thank all our contributing investigators and study participants who make this research possible. We acknowledge Dr E Jane Costello for leadership in collecting and characterising the Gene-Environment-Development Initiative–Great Smoky Mountains Study sample and her valuable insights on the development of this study and interpretation of findings. This research was done using the UK Biobank Resource, application numbers 4844 and 58146. Individual funding was provided by the following grants: MH109532 (AA, HJE, JG); F32AA027435 (ECJ); K02DA032573 (AA); 1U01MH109514-01 (ADB); 5T32DA007261 (AH); T32MH018951 (DAAB); NIH F32 MH122058 (FRW); Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (ADB); the European Commission, Horizon 2020, grant number 667302 (ADB); R01-DA034076 (TET); R01HD060726 (BWD, KMH, JDB, MBM); Health Research Council of New Zealand 16/600 (JB, JHo, MAK, JFP); Health Research Council of New Zealand 11/792 (JB, JHo); AA027827, AG061162 (RB); U24DA041147 (SAB); R01HD093651, R01MH117559, P30DA023026 (WEC); DA011015, DA038504 (RPC); K02 AA018755 (DMD); P01-HD031921, R01-HD073342 (KMH);R01 DA018673, DA025109, DA024413, DA016977 (HHM); Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z), UKRI MRC (MC_PC_17209, MR/S035818/1) (AMM); K01MH113848, The Brain & Behavior Research Foundation NARSAD grant 28632 (REP); R21 DA047527, R21 DC018098 (RP); SAMHSA Grant # 1H79TI081668 (MDR); R01DA026911, R21DA046791 (NLS); R01HD050735, U54EB020403 (subaward), NHMRC Australia (496682; 1009064) (MJW); Tobacco-Related Disease Research Program of the University of California Grant Number T29KT0526, Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant #27676 (SS-R). The iPSYCH team was supported by grants from the Lundbeck Foundation (R165–2013–15320, R102-A9118, R155–2014–1724, and R248–2017–2003), the European Commission (Horizon 2020, grant number 667302), and the universities and university hospitals of Aarhus and Copenhagen, Denmark. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. Data handling and analysis on the GenomeDK HPC facility was supported by NIMH (1U01MH109514–01 to ADB). High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Work at deCODE genetics was partly funded by the NIDA (R01−DA034076). The BioVU dataset(s) used for the PheWAS analyses described were obtained from Vanderbilt University Medical Center's BioVU, which is supported by numerous sources: institutional funding, private agencies, and federal grants. These grants include the NIH funded Shared Instrumentation Grant S10RR025141, and Clinical Translational Sciences Award grants UL1TR002243, UL1TR000445, and UL1RR024975. Genomic data are also supported by investigator-led projects that include U01HG004798, R01NS032830, RC2GM092618, P50GM115305, U01HG006378, U19HL065962, and R01HD074711, and additional funding sources https://victr.vumc.org/biovu-funding/]. Dr Degenhardt is funded by the NIH (R01 DA144740) and the Australian National Health and Medical Research Council Research (1135991). Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive Development (ABCD) Study, held in the NIMH Data Archive. The ABCD Study is supported by the NIH and additional federal partners under award numbers U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, and U01DA041025. A listing of participating sites and a complete listing of the study investigators can be found online. ABCD consortium investigators designed and implemented the study or provided data, or both, but did not necessarily participate in analysis or writing of this study. This manuscript reflects the views of the authors and might not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this study came from the NIMH Data Archive 2.0.1. Funding support for the Comorbidity and Trauma Study (dbGAP accession number, phs000277.v1.p1) was provided by NIDA (R01 DA17305); GWAS genotyping services at the Center for Inherited Disease Research at The Johns Hopkins University were supported by NIH (contract N01-HG-65403). Funding support for the Center for Education and Drug Abuse Research (dbGAP accession number, phs001649.v1.p1) was provided by NIDA (P50 DA005605). The Christchurch Health and Development Study has been supported by funding from the Health Research Council of New Zealand, 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, US NIH grant MH077874, and NIDA grant, a developmental model of gene-environment interplay in substance use disorders (R01DA024413) 2007–12. The Collaborative Study on the Genetics of Alcoholism (COGA; Principal Investigators B Porjesz, V Hesselbrock, and T Foroud; Scientific Director, A Agrawal; Translational Director, D Dick) includes 11 different centres: University of Connecticut (V Hesselbrock); Indiana University (H J Edenberg, T Foroud, J Nurnberger Jr, Y Liu); University of Iowa (S Kuperman, J Kramer); SUNY Downstate (B Porjesz, J Meyers, C Kamarajan, A Pandey); Washington University in St Louis (L Bierut, J Rice, K Bucholz, A Agrawal); University of California at San Diego (M Schuckit); Rutgers University (J Tischfield, A Brooks, R Hart); The Children's Hospital of Philadelphia, University of Pennsylvania (L Almasy); Virginia Commonwealth University (D Dick, J Salvatore); Icahn School of Medicine at Mount Sinai (A Goate, M Kapoor, P Slesinger); and Howard University (D Scott). Other COGA collaborators include L Bauer (University of Connecticut); L Wetherill, X Xuei, D Lai, S O'Connor, M Plawecki, S Lourens (Indiana University); L Acion (University of Iowa); G Chan (University of Iowa; University of Connecticut); D B Chorlian, J Zhang, S Kinreich, G Pandey (SUNY Downstate); M Chao (Icahn School of Medicine at Mount Sinai); A Anokhin, V McCutcheon, S Saccone (Washington University); F Aliev, P Barr (Virginia Commonwealth University); and H Chin, and A Parsian (NIAAA Staff Collaborators). We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding Principal Investigator and Co-Principal Investigator of COGA, and also owe a debt of gratitude to other past organisers of COGA, including Ting-Kai Li, P Michael Conneally, Raymond Crowe, and Wendy Reich for their crucial contributions. This national collaborative study is supported by NIH Grant U10AA008401 from NIAAA and NIDA. We thank Kim Doheny and Elizabeth Pugh from the Center for Inherited Disease Research and Justin Paschall from the NCBI dbGaP staff for valuable assistance with genotyping and quality control in developing the dataset available at dbGaP (phs000125.v1.p1, phs000763.v1.p1, phs000976.v1.p1). Support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative (GEI; U01 HG004422; dbGaP study accession phs000092.v1.p1). SAGE is one of the GWAS funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonisation and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by COGA (U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (P01 CA089392; see also phs000404.v1.p1), and the Family Study of Cocaine Dependence (R01 DA013423, R01 DA019963). Funding support for genotyping, which was done at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), NIAAA, NIDA, and the NIH contract High throughput genotyping for studying the genetic contributions to human disease (HHSN268200782096C). The Great Smoky Mountains Study project (phs000852.v1.p1) was supported by NIDA (U01DA024413, R01DA11301), NIMH (R01MH063970, R01MH063671, R01MH048085, K01MH093731, and K23MH080230), NARSAD, and the William T Grant Foundation. We are grateful to all the Great Smoky Mountains Study and Caring for Children in the Community study participants who contributed to this work. The following grants supported data collection and analysis of Center on Antisocial Drug Dependence (dbGAP in progress): DA011015, DA012845, DA021913, DA021905, DA032555, and DA035804. Alcohol Dependence in African Americans was funded by NIH grant R01 AA017444. Brisbane Longitudinal Twin Study was supported by the US NIDA (R00DA023549), and by the Australian Research Council (DP0343921, DP0664638, 464914, 619667, FT110100548). Gene-Environment-Development Initiative Virginia Commonwealth University (VTSABD; dbGAP in progress) was supported by NIDA (U01DA024413, R01DA025109), NIMH (R01MH045268, R01MH055557, R01MH068521), and the Virginia Tobacco Settlement Foundation, grant 8520012. We are grateful to all the Virginia Twin Studies of Adolescent Behavioral Development, Young Adult Follow-Up, Transitions to Substance Use study participants who contributed to this work. Minnesota Center for Twin and Family Research (phs000620.v1.p1) contributing to this publication was supported by the NIH under award numbers DA005147, DA013240, DA024417, DA036216, AA009367, MH066140, DA042755, DA037904, HG008983, and DA044283. Funding for Substance Use Disorder Liability: Candidate System Genes study was supported by R01 DA019157 and P50 DA005605. Yale-Penn (phs000425.v1.p1; phs000952.v1.p1) was supported by NIH grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, and R01 AA017535 and the Veterans Affairs Connecticut and Philadelphia Veterans Affairs Mental Illness Research, Educational, and Clinical Centers. Australian Alcohol and Nicotine studies (OZ-ALC-NAG; phs000181.v1.p1) were supported by NIH grants AA07535,AA07728, AA13320, AA13321, AA14041, AA11998, AA17688, DA012854, and DA019951, by grants from the Australian National Health and Medical Research Council (241944, 339462, 389927,389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, and 552498), by grants from the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016, and DP0343921); and by the 5th Framework Programme (FP-5) GenomEUtwin Project (QLG2-CT-2002–01254). GWAS genotyping at Center for Inherited Disease Research was supported by a grant to the late Richard Todd, MD, PhD, former Principal Investigator of grant AA13320. Irish Affected Sib-Pair Study of Alcohol Dependence GWAS data collection and analysis was supported by NIAAA grants P20-AA-017828 and P50-AA-022537. Sample collection was supported by R01-AA-011408. Control genotyping was supported by NIMH grant R01-MH-083094 and Wellcome Trust Case Control Consortium 2 grant WTCCC-084710. This research uses data from Add Health, a programme project directed by Kathleen Mullan Harris and designed by J Richard Udry, Peter S Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. No direct support was received from grant P01-HD31921 for this analysis. We additionally thank the groups who directly shared GWAS results. We would like to acknowledge all participating groups of the International Cannabis Consortium, and in particular the members of the working group including Sven Stringer, Camelia Minica, Karin Verweij, Hamdi Mbarek, Eske Derks, Nathan Gillespie, and Jacqueline Vink. We also wish to thank the ENIGMA consortium for providing GWAS results on subcortical brain volumes. Finally, we acknowledge the valuable contribution of groups who have publicly released summary statistics from their respective GWAS. Specifically, thanks to researchers from Schumann and colleagues (2016) including the CHARGE+ and AlcGen consortia and to all members of Psychiatric Genomics Consortium (PGC). Individual-level data from the genotyped cohorts and cohort-level summary statistics will be made available to researchers following an approved analysis proposal through the PGC Substance Use Disorder group with agreement of the cohort Principal Investigators; contact the corresponding authors for details. Some cohort data are also available from dbGaP except when prohibited by Institutional Review Board, funding requirements or European Union data restrictions (accession numbers: phs000277.v1.p1, phs000092.v1.p1, phs000852.v1.p1, phs000404.v1.p1, phs000092.v1.p1, phs000620.v1.p1, phs001649.v1.p1, phs000425.v1.p1, phs000181.v1.p1, phs000763.v1.p1, phs000125.v1.p1).

Funders	Funder number
University of Otago
University of Connecticut
Washington University in St. Louis
Families for Borderline Personality Disorder Research
Carney Centre for Pharmacogenomics
Virginia Commonwealth University
Johns Hopkins University
Lotto New Zealand
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Aarhus Universitet
AlcGen consortia
University of California, San Diego
Rutgers, The State University of New Jersey
Indiana University
universities and university hospitals of Aarhus and Copenhagen
State University of New York
European Commission
COGA
Icahn School of Medicine at Mount Sinai
Genetics of Alcoholism
University of Iowa
International Cannabis Consortium
Canterbury Medical Research Foundation
Gene Environment Association Studies
Horizon 2020
National Child Health Research Foundation
Howard University	U10 AA008401, U01 HG004422
National Human Genome Research Institute	N01HG065403, U01HG006378, U01HG004798, U01HG004446, U01HG004422, R01HG008983, U01HG004438
National Institute on Drug Abuse	P60DA011015, R01DA025109, R01DA026911, U01DA041106, R01DA024413, R37DA005147, U01DA041028, U01DA041148, U01DA041025, U01DA041022, R00DA023549, R01DA021905, K02DA032573, R01DA011301, R21DA047527, U01DA024417, T32DA007261, K08DA019951, U24DA041123, U01DA041134, P30DA023026, U01DA041174, R01DA013240, R21DA046791, U01DA041093, R01DA036216, RC2DA028909, R01DA012849, R01DA037904, R01DA035804, R01DA044283, R01DA012845, R01DA019157, U01DA041048, U01DA041089, R01DA034076, U01DA041120, R21DA038504, R01DA012854, U01DA051038, K24DA032555, R01DA013423, P50DA005605, R01DA017305, R01DA016977, R01DA018673, U01DA041117, R01DA019963, U24DA041147, R01DA018432, U01DA041156, R01DA042755, R01DA021913, R01DA012690
National Health and Medical Research Council	389927,389875, A7960034, 496682, 339462, A79801419, 389892, 389891, 552485, 241944, DP0770096, 442981, 552498, 496739, DP0212016, 442915, 389938, 1009064, A79906588
National Institute on Aging	R01AG061162
National Institute on Alcohol Abuse and Alcoholism	R01AA011330, R37AA007728, R01AA017535, R01AA013320, R01AA009367, P50AA011998, R01AA017444, R01AA013321, U10AA008401, F32AA027435, R01AA011408, P20AA017828, R21AA027827, R01AA007535, 58146, K05AA017688, K02AA018755, P50AA022537, R01AA014041, 4844
National Institute of Mental Health	K23MH080230, R01MH063671, R01MH068521, R01MH063970, U01MH109514, R01MH123619, R56MH120736, U01MH109532, K01MH093731, K01MH113848, R01MH117559, T32MH018951, R01MH077874, F32MH122058, R01MH048085, R01MH083094, R01MH066140
National Institute of Child Health and Human Development	R01HD060726, P2CHD066613, P01HD031921, R01HD073342, R01HD093651, R01HD050735, R03HD097630, R01HD074711
Novo Nordisk Fonden	R01−DA034076, 1U01MH109514–01
Substance Abuse and Mental Health Services Administration	R01DA026911, 1H79TI081668, R01HD050735, U54EB020403, R21DA046791
US NIDA	R00DA023549
Australian National Health and Medical Research Council Research	N01-HG-65403, R01 DA17305, U01DA041106, U01DA041117, U01DA041028, U01DA041148, U01DA041048, U24DA041123, U01DA041025, U01DA041156, U01DA041134, U01DA041089, U01DA041022, 1135991, U01DA041120, U01DA041174, U01DA041093
National Center for Research Resources	S10RR025141, UL1RR024975
Center for Education and Drug Abuse Research	P50 DA005605
National Alliance for Research on Schizophrenia and Depression	27676
Wellcome Trust	104036/Z/14/Z, 216767/Z/19/Z
Australian Research Council	R01DA025109, FT110100548, R01MH055557, DP0664638, R01MH068521, 464914, R01MH045268, DP0343921, 619667
National Cancer Institute	P01CA089392
Health Research Council of New Zealand	16/600, DA025109, P01-HD031921, DA024413, 11/792, R01HD093651, AA027827, U24DA041147, R01MH117559, DA011015, DA038504, AG061162, DA016977, R01-HD073342, P30DA023026, K02 AA018755, R01 DA018673
Tobacco-Related Disease Research Program of the University of California	T29KT0526
National Institute of General Medical Sciences	RC2GM092618, P50GM115305
Lundbeck Foundation	R165–2013–15320, R248–2017–2003, R155–2014–1724, R102-A9118
European Commission, Horizon 2020	R01HD060726
Brain and Behavior Research Foundation	R21 DA047527, R21 DC018098, 28632
UKRI MRC	K01MH113848, MR/S035818/1, MC_PC_17209
Vanderbilt University Medical Center	R01 DA144740, U01HG006378, R01NS032830, U19HL065962, RC2GM092618, U01HG004798, UL1TR000445, S10RR025141, UL1RR024975, P50GM115305, UL1TR002243, R01HD074711
Wellcome Trust Case Control Consortium 2	WTCCC-084710, P01-HD31921
National Institutes of Health	HHSN268200782096C
National Center for Advancing Translational Sciences	UL1TR000445, UL1TR002243
National Center for Biotechnology Information	R01 DA013423, P01 CA089392, R01 DA019963
National Heart, Lung, and Blood Institute	U19HL065962
National Institute of Biomedical Imaging and Bioengineering	U54EB020403
Virginia Tobacco Settlement Foundation	DA019951, R01 DA12690, DA013240, DA024417, R01 DA18432, DA042755, AA07728, R01 AA11330, HG008983, MH066140, AA07535, DA037904, R01 DA12849, AA009367, 8520012, DA036216, DA012854, R01 AA017535, DA005147, RC2 DA028909, DA044283, R01 DA019157
Horizon 2020 Framework Programme	667302
James Hume Bequest Fund	R01DA024413, MH077874
National Institute on Deafness and Other Communication Disorders	R21DC018098
GENEVA Coordinating Center	U01 HG004446
Fifth Framework Programme	QLG2-CT-2002–01254, R01-AA-011408, FP-5, R01-MH-083094, P50-AA-022537, P20-AA-017828
National Institute of Neurological Disorders and Stroke	R01NS032830

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@article{a45ceb7e9c144989b4d946bc7035df4d,

title = "A large-scale genome-wide association study meta-analysis of cannabis use disorder",

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.Funding: 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. ",

author = "Emma Johnson and Ditte Demontis and Thorgeirsson, \{Thorgeir E\} and Walters, \{Raymond K\} and Renato Polimanti and Hatoum, \{Alexander S\} and Sandra Sanchez-roige and Paul, \{Sarah E\} and Wendt, \{Frank R\} and Toni-kim Clarke and Dongbing Lai and Reginsson, \{Gunnar W\} and Hang Zhou and June He and Baranger, \{David A A\} and Gudbjartsson, \{Daniel F\} and Robbee Wedow and Daniel Adkins and Amy Adkins and Jeffry Alexander and Silviu-alin Bacanu and Bigdeli, \{Tim B\} and Joseph Boden and Sandra Brown and Kathleen Bucholz and Jonas Bybjerg-grauholm and Corley, \{Robin P\} and Louisa Degenhardt and Danielle Dick and Benjamin Domingue and Louis Fox and Alison Goate and Scott Gordon and Laura Hack and Dana Hancock and Sarah Hartz and Hickie, \{Ian B\} and Hougaard, \{David M\} and Kenneth Krauter and Penelope Lind and Jeanette Mcclintick and Matthew Mcqueen and Jacquelyn Meyers and Grant Montgomery and Ole Mors and Mortensen, \{Preben B\} and Merete Nordentoft and John Pearson and Roseann Peterson and Maureen Reynolds and John Rice and Valgerdur Runarsdottir and Nancy Saccone and Richard Sherva and Judy Silberg and Ralph Tarter and Thorarinn Tyrfingsson and Tamara Wall and Bradley Webb and Thomas Werge and Leah Wetherill and Wright, \{Margaret J\} and Stephanie Zellers and Mark Adams and Laura Bierut and Jason Boardman and William Copeland and Lindsay Farrer and Tatiana Foroud and Nathan Gillespie and Richard Grucza and Harris, \{Kathleen Mullan\} and Andrew Heath and Victor Hesselbrock and John Hewitt and Christian Hopfer and John Horwood and William Iacono and Eric Johnson and Kenneth Kendler and Martin Kennedy and Henry Kranzler and Pamela Madden and Hermine Maes and Brion Maher and Nicholas Martin and Matthew Mcgue and Andrew Mcintosh and Sarah Medland and Nelson, \{Elliot C\} and Bernice Porjesz and Brien Riley and Michael Stallings and Michael Vanyukov and Scott Vrieze and Davis, \{Lea K\} and Ryan Bogdan and Joel Gelernter and Howard Edenberg and Kari Stefansson and B{\o}rglum, \{Anders D\} and Arpana Agrawal and Walters, \{Raymond K\} and Renato Polimanti and Emma Johnson and Jeanette Mcclintick and Alexander Hatoum and June He and Frank Wendt and Hang Zhou and Mark Adams and Amy Adkins and Fazil Aliev and Silviu-alin Bacanu and Anthony Batzler and Sarah Bertelsen and Joanna Biernacka and Tim Bigdeli and Li-shiun Chen and Toni-kim Clarke and Yi-ling Chou and Franziska Degenhardt and Anna Docherty and Alexis Edwards and Pierre Fontanillas and Jerome Foo and Louis Fox and Josef Frank and Ina Giegling and Scott Gordon and Laura Hack and Annette Hartmann and Sarah Hartz and Stefanie Heilmann-heimbach and Stefan Herms and Colin Hodgkinson and Per Hoffman and Jouke Hottenga and Martin Kennedy and Mervi Alanne-kinnunen and Bettina Konte and Jari Lahti and Marius Lahti-pulkkinen and Dongbing Lai and Lannie Ligthart and Anu Loukola and Brion Maher and Hamdi Mbarek and Andrew Mcintosh and Matthew Mcqueen and Jacquelyn Meyers and Yuri Milaneschi and Teemu Palviainen and John Pearson and Roseann Peterson and Samuli Ripatti and Euijung Ryu and Nancy Saccone and Jessica Salvatore and Sandra Sanchez-roige and Melanie Schwandt and Richard Sherva and Fabian Streit and Jana Strohmaier and Nathaniel Thomas and Jen-chyong Wang and Bradley Webb and Robbee Wedow and Leah Wetherill and Amanda Wills and Jason Boardman and Danfeng Chen and Doo-sup Choi and William Copeland and Robert Culverhouse and Norbert Dahmen and Louisa Degenhardt and Benjamin Domingue and Sarah Elson and Mark Frye and Wolfgang G{\"a}bel and Caroline Hayward and Marcus Ising and Margaret Keyes and Falk Kiefer and John Kramer and Samuel Kuperman and Susanne Lucae and Michael Lynskey and Wolfgang Maier and Karl Mann and Satu M{\"a}nnist{\"o} and Bertram M{\"u}ller-myhsok and Alison Murray and John Nurnberger and Aarno Palotie and Ulrich Preuss and Katri R{\"a}ikk{\"o}nen and Maureen Reynolds and Monika Ridinger and Norbert Scherbaum and Marc Schuckit and Michael Soyka and Jens Treutlein and Stephanie Witt and Norbert Wodarz and Peter Zill and Daniel Adkins and Joseph Boden and Dorret Boomsma and Laura Bierut and Sandra Brown and Kathleen Bucholz and Sven Cichon and Costello, \{E. Jane\} and \{De Wit\}, Harriet and Nancy Diazgranados and Danielle Dick and Johan Eriksson and Lindsay Farrer and Tatiana Foroud and Nathan Gillespie and Alison Goate and David Goldman and Richard Grucza and Dana Hancock and Harris, \{Kathleen Mullan\} and Andrew Heath and Victor Hesselbrock and John Hewitt and Christian Hopfer and John Horwood and William Iacono and Eric Johnson and Jaakko Kaprio and Victor Karpyak and Kenneth Kendler and Henry Kranzler and Kenneth Krauter and Paul Lichtenstein and Penelope Lind and Matt Mcgue and James Mackillop and Pamela Madden and Hermine Maes and Patrik Magnusson and Nicholas Martin and Sarah Medland and Grant Montgomery and Elliot Nelson and Markus N{\"o}then and Abraham Palmer and Nancy Pederson and Brenda Penninx and Bernice Porjesz and John Rice and Marcella Rietschel and Brien Riley and Richard Rose and Dan Rujescu and Pei-hong Shen and Judy Silberg and Michael Stallings and Ralph Tarter and Michael Vanyukov and Scott Vrieze and Tamara Wall and John Whitfield and Hongyu Zhao and Benjamin Neale and Joel Gelernter and Howard Edenberg and Arpana Agrawal and \{Psychiatric Genomics Consortium Substance Use Disorders Workgroup\}",

year = "2020",

month = dec,

doi = "10.1016/S2215-0366(20)30339-4",

language = "English",

volume = "7",

pages = "1032--1045",

journal = "The Lancet Psychiatry",

issn = "2215-0366",

publisher = "Elsevier Ltd",

number = "12",

}

TY - JOUR

T1 - A large-scale genome-wide association study meta-analysis of cannabis use disorder

AU - Johnson, Emma

AU - Demontis, Ditte

AU - Thorgeirsson, Thorgeir E

AU - Walters, Raymond K

AU - Polimanti, Renato

AU - Hatoum, Alexander S

AU - Sanchez-roige, Sandra

AU - Paul, Sarah E

AU - Wendt, Frank R

AU - Clarke, Toni-kim

AU - Lai, Dongbing

AU - Reginsson, Gunnar W

AU - Zhou, Hang

AU - He, June

AU - Baranger, David A A

AU - Gudbjartsson, Daniel F

AU - Wedow, Robbee

AU - Adkins, Daniel

AU - Adkins, Amy

AU - Alexander, Jeffry

AU - Bacanu, Silviu-alin

AU - Bigdeli, Tim B

AU - Boden, Joseph

AU - Brown, Sandra

AU - Bucholz, Kathleen

AU - Bybjerg-grauholm, Jonas

AU - Corley, Robin P

AU - Degenhardt, Louisa

AU - Dick, Danielle

AU - Domingue, Benjamin

AU - Fox, Louis

AU - Goate, Alison

AU - Gordon, Scott

AU - Hack, Laura

AU - Hancock, Dana

AU - Hartz, Sarah

AU - Hickie, Ian B

AU - Hougaard, David M

AU - Krauter, Kenneth

AU - Lind, Penelope

AU - Mcclintick, Jeanette

AU - Mcqueen, Matthew

AU - Meyers, Jacquelyn

AU - Montgomery, Grant

AU - Mors, Ole

AU - Mortensen, Preben B

AU - Nordentoft, Merete

AU - Pearson, John

AU - Peterson, Roseann

AU - Reynolds, Maureen

AU - Rice, John

AU - Runarsdottir, Valgerdur

AU - Saccone, Nancy

AU - Sherva, Richard

AU - Silberg, Judy

AU - Tarter, Ralph

AU - Tyrfingsson, Thorarinn

AU - Wall, Tamara

AU - Webb, Bradley

AU - Werge, Thomas

AU - Wetherill, Leah

AU - Wright, Margaret J

AU - Zellers, Stephanie

AU - Adams, Mark

AU - Bierut, Laura

AU - Boardman, Jason

AU - Copeland, William

AU - Farrer, Lindsay

AU - Foroud, Tatiana

AU - Gillespie, Nathan

AU - Grucza, Richard

AU - Harris, Kathleen Mullan

AU - Heath, Andrew

AU - Hesselbrock, Victor

AU - Hewitt, John

AU - Hopfer, Christian

AU - Horwood, John

AU - Iacono, William

AU - Johnson, Eric

AU - Kendler, Kenneth

AU - Kennedy, Martin

AU - Kranzler, Henry

AU - Madden, Pamela

AU - Maes, Hermine

AU - Maher, Brion

AU - Martin, Nicholas

AU - Mcgue, Matthew

AU - Mcintosh, Andrew

AU - Medland, Sarah

AU - Nelson, Elliot C

AU - Porjesz, Bernice

AU - Riley, Brien

AU - Stallings, Michael

AU - Vanyukov, Michael

AU - Vrieze, Scott

AU - Davis, Lea K

AU - Bogdan, Ryan

AU - Gelernter, Joel

AU - Edenberg, Howard

AU - Stefansson, Kari

AU - Børglum, Anders D

AU - Agrawal, Arpana

AU - Walters, Raymond K

AU - Polimanti, Renato

AU - Johnson, Emma

AU - Mcclintick, Jeanette

AU - Hatoum, Alexander

AU - He, June

AU - Wendt, Frank

AU - Zhou, Hang

AU - Adams, Mark

AU - Adkins, Amy

AU - Aliev, Fazil

AU - Bacanu, Silviu-alin

AU - Batzler, Anthony

AU - Bertelsen, Sarah

AU - Biernacka, Joanna

AU - Bigdeli, Tim

AU - Chen, Li-shiun

AU - Clarke, Toni-kim

AU - Chou, Yi-ling

AU - Degenhardt, Franziska

AU - Docherty, Anna

AU - Edwards, Alexis

AU - Fontanillas, Pierre

AU - Foo, Jerome

AU - Fox, Louis

AU - Frank, Josef

AU - Giegling, Ina

AU - Gordon, Scott

AU - Hack, Laura

AU - Hartmann, Annette

AU - Hartz, Sarah

AU - Heilmann-heimbach, Stefanie

AU - Herms, Stefan

AU - Hodgkinson, Colin

AU - Hoffman, Per

AU - Hottenga, Jouke

AU - Kennedy, Martin

AU - Alanne-kinnunen, Mervi

AU - Konte, Bettina

AU - Lahti, Jari

AU - Lahti-pulkkinen, Marius

AU - Lai, Dongbing

AU - Ligthart, Lannie

AU - Loukola, Anu

AU - Maher, Brion

AU - Mbarek, Hamdi

AU - Mcintosh, Andrew

AU - Mcqueen, Matthew

AU - Meyers, Jacquelyn

AU - Milaneschi, Yuri

AU - Palviainen, Teemu

AU - Pearson, John

AU - Peterson, Roseann

AU - Ripatti, Samuli

AU - Ryu, Euijung

AU - Saccone, Nancy

AU - Salvatore, Jessica

AU - Sanchez-roige, Sandra

AU - Schwandt, Melanie

AU - Sherva, Richard

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Thomas, Nathaniel

AU - Wang, Jen-chyong

AU - Webb, Bradley

AU - Wedow, Robbee

AU - Wetherill, Leah

AU - Wills, Amanda

AU - Boardman, Jason

AU - Chen, Danfeng

AU - Choi, Doo-sup

AU - Copeland, William

AU - Culverhouse, Robert

AU - Dahmen, Norbert

AU - Degenhardt, Louisa

AU - Domingue, Benjamin

AU - Elson, Sarah

AU - Frye, Mark

AU - Gäbel, Wolfgang

AU - Hayward, Caroline

AU - Ising, Marcus

AU - Keyes, Margaret

AU - Kiefer, Falk

AU - Kramer, John

AU - Kuperman, Samuel

AU - Lucae, Susanne

AU - Lynskey, Michael

AU - Maier, Wolfgang

AU - Mann, Karl

AU - Männistö, Satu

AU - Müller-myhsok, Bertram

AU - Murray, Alison

AU - Nurnberger, John

AU - Palotie, Aarno

AU - Preuss, Ulrich

AU - Räikkönen, Katri

AU - Reynolds, Maureen

AU - Ridinger, Monika

AU - Scherbaum, Norbert

AU - Schuckit, Marc

AU - Soyka, Michael

AU - Treutlein, Jens

AU - Witt, Stephanie

AU - Wodarz, Norbert

AU - Zill, Peter

AU - Adkins, Daniel

AU - Boden, Joseph

AU - Boomsma, Dorret

AU - Bierut, Laura

AU - Brown, Sandra

AU - Bucholz, Kathleen

AU - Cichon, Sven

AU - Costello, E. Jane

AU - De Wit, Harriet

AU - Diazgranados, Nancy

AU - Dick, Danielle

AU - Eriksson, Johan

AU - Farrer, Lindsay

AU - Foroud, Tatiana

AU - Gillespie, Nathan

AU - Goate, Alison

AU - Goldman, David

AU - Grucza, Richard

AU - Hancock, Dana

AU - Harris, Kathleen Mullan

AU - Heath, Andrew

AU - Hesselbrock, Victor

AU - Hewitt, John

AU - Hopfer, Christian

AU - Horwood, John

AU - Iacono, William

AU - Johnson, Eric

AU - Kaprio, Jaakko

AU - Karpyak, Victor

AU - Kendler, Kenneth

AU - Kranzler, Henry

AU - Krauter, Kenneth

AU - Lichtenstein, Paul

AU - Lind, Penelope

AU - Mcgue, Matt

AU - Mackillop, James

AU - Madden, Pamela

AU - Maes, Hermine

AU - Magnusson, Patrik

AU - Martin, Nicholas

AU - Medland, Sarah

AU - Montgomery, Grant

AU - Nelson, Elliot

AU - Nöthen, Markus

AU - Palmer, Abraham

AU - Pederson, Nancy

AU - Penninx, Brenda

AU - Porjesz, Bernice

AU - Rice, John

AU - Rietschel, Marcella

AU - Riley, Brien

AU - Rose, Richard

AU - Rujescu, Dan

AU - Shen, Pei-hong

AU - Silberg, Judy

AU - Stallings, Michael

AU - Tarter, Ralph

AU - Vanyukov, Michael

AU - Vrieze, Scott

AU - Wall, Tamara

AU - Whitfield, John

AU - Zhao, Hongyu

AU - Neale, Benjamin

AU - Gelernter, Joel

AU - Edenberg, Howard

AU - Agrawal, Arpana

AU - Psychiatric Genomics Consortium Substance Use Disorders Workgroup

PY - 2020/12

Y1 - 2020/12

N2 - 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.Funding: 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.

AB - 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.Funding: 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.

UR - https://www.scopus.com/pages/publications/85095443055

UR - https://www.scopus.com/pages/publications/85095443055#tab=citedBy

U2 - 10.1016/S2215-0366(20)30339-4

DO - 10.1016/S2215-0366(20)30339-4

M3 - Article

SN - 2215-0366

VL - 7

SP - 1032

EP - 1045

JO - The Lancet Psychiatry

JF - The Lancet Psychiatry

IS - 12

ER -

A large-scale genome-wide association study meta-analysis of cannabis use disorder

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