Literature DB >> 30150663

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Joëlle A Pasman1, Karin J H Verweij1,2, Zachary Gerring3, Sven Stringer4, Sandra Sanchez-Roige5, Jorien L Treur6, Abdel Abdellaoui2, Michel G Nivard7, Bart M L Baselmans7, Jue-Sheng Ong3, Hill F Ip7, Matthijs D van der Zee7, Meike Bartels7, Felix R Day8, Pierre Fontanillas9, Sarah L Elson9, Harriet de Wit10, Lea K Davis11, James MacKillop12, Jaime L Derringer13, Susan J T Branje14, Catharina A Hartman15, Andrew C Heath16, Pol A C van Lier17, Pamela A F Madden16, Reedik Mägi18, Wim Meeus14, Grant W Montgomery19, A J Oldehinkel15, Zdenka Pausova20, Josep A Ramos-Quiroga21,22,23,24, Tomas Paus25,26, Marta Ribases21,22,23, Jaakko Kaprio27, Marco P M Boks28, Jordana T Bell29, Tim D Spector29, Joel Gelernter30, Dorret I Boomsma7, Nicholas G Martin3, Stuart MacGregor3, John R B Perry8, Abraham A Palmer5,31, Danielle Posthuma4, Marcus R Munafò6,32, Nathan A Gillespie3,33, Eske M Derks3, Jacqueline M Vink34.   

Abstract

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

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Year:  2018        PMID： 30150663      PMCID： PMC6386176          DOI： 10.1038/s41593-018-0206-1

Source DB:  PubMed          Journal:  Nat Neurosci        ISSN： 1097-6256            Impact factor:   24.884


  67 in total

1.  Adverse health effects of marijuana use.

Authors:  Nora D Volkow; Wilson M Compton; Susan R B Weiss
Journal:  N Engl J Med       Date:  2014-08-28       Impact factor: 91.245

2.  The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation.

Authors:  Karin J H Verweij; Anna A E Vinkhuyzen; Beben Benyamin; Michael T Lynskey; Lydia Quaye; Arpana Agrawal; Scott D Gordon; Grant W Montgomery; Pamela A F Madden; Andrew C Heath; Timothy D Spector; Nicholas G Martin; Sarah E Medland
Journal:  Addict Biol       Date:  2012-07-24       Impact factor: 4.280

3.  GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

Authors:  D A Bennett; I J Deary; M A Ikram; L J Launer; A L Fitzpatrick; S Seshadri; C M van Duijn; T H Mosley; C A Ibrahim-Verbaas; J Bressler; S Debette; M Schuur; A V Smith; J C Bis; G Davies; S Trompet; J A Smith; C Wolf; L B Chibnik; Y Liu; V Vitart; M Kirin; K Petrovic; O Polasek; L Zgaga; C Fawns-Ritchie; P Hoffmann; J Karjalainen; J Lahti; D J Llewellyn; C O Schmidt; K A Mather; V Chouraki; Q Sun; S M Resnick; L M Rose; C Oldmeadow; M Stewart; B H Smith; V Gudnason; Q Yang; S S Mirza; J W Jukema; P L deJager; T B Harris; D C Liewald; N Amin; L H Coker; O Stegle; O L Lopez; R Schmidt; A Teumer; I Ford; N Karbalai; J T Becker; M K Jonsdottir; R Au; Rsn Fehrmann; S Herms; M Nalls; W Zhao; S T Turner; K Yaffe; K Lohman; J C van Swieten; Slr Kardia; D S Knopman; W M Meeks; G Heiss; E G Holliday; P W Schofield; T Tanaka; D J Stott; J Wang; P Ridker; A J Gow; A Pattie; J M Starr; L J Hocking; N J Armstrong; S McLachlan; J M Shulman; L C Pilling; G Eiriksdottir; R J Scott; N A Kochan; A Palotie; Y-C Hsieh; J G Eriksson; A Penman; R F Gottesman; B A Oostra; L Yu; A L DeStefano; A Beiser; M Garcia; J I Rotter; M M Nöthen; A Hofman; P E Slagboom; Rgj Westendorp; B M Buckley; P A Wolf; A G Uitterlinden; B M Psaty; H J Grabe; S Bandinelli; D I Chasman; F Grodstein; K Räikkönen; J-C Lambert; D J Porteous; J F Price; P S Sachdev; L Ferrucci; J R Attia; I Rudan; C Hayward; A F Wright; J F Wilson; S Cichon; L Franke; H Schmidt; J Ding; Ajm de Craen; M Fornage
Journal:  Mol Psychiatry       Date:  2015-04-14       Impact factor: 15.992

4.  TTC12-ANKK1-DRD2 and CHRNA5-CHRNA3-CHRNB4 influence different pathways leading to smoking behavior from adolescence to mid-adulthood.

Authors:  Francesca Ducci; Marika Kaakinen; Anneli Pouta; Anna-Liisa Hartikainen; Juha Veijola; Matti Isohanni; Pimphen Charoen; Lachlan Coin; Clive Hoggart; Jesper Ekelund; Leena Peltonen; Nelson Freimer; Paul Elliott; Gunter Schumann; Marjo-Riitta Järvelin
Journal:  Biol Psychiatry       Date:  2010-12-17       Impact factor: 13.382

5.  The cell adhesion molecules N-cadherin and neural cell adhesion molecule regulate human growth hormone: a novel mechanism for regulating pituitary hormone secretion.

Authors:  Tami Rubinek; Run Yu; Moshe Hadani; Gad Barkai; Dvora Nass; Shlomo Melmed; Ilan Shimon
Journal:  J Clin Endocrinol Metab       Date:  2003-08       Impact factor: 5.958

6.  Quality control and conduct of genome-wide association meta-analyses.

Authors:  Thomas W Winkler; Felix R Day; Damien C Croteau-Chonka; Andrew R Wood; Adam E Locke; Reedik Mägi; Teresa Ferreira; Tove Fall; Mariaelisa Graff; Anne E Justice; Jian'an Luan; Stefan Gustafsson; Joshua C Randall; Sailaja Vedantam; Tsegaselassie Workalemahu; Tuomas O Kilpeläinen; André Scherag; Tonu Esko; Zoltán Kutalik; Iris M Heid; Ruth J F Loos
Journal:  Nat Protoc       Date:  2014-04-24       Impact factor: 13.491

7.  Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression.

Authors:  Jack Bowden; George Davey Smith; Stephen Burgess
Journal:  Int J Epidemiol       Date:  2015-06-06       Impact factor: 7.196

8.  The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription.

Authors:  Z R Donaldson; B le Francois; T L Santos; L M Almli; M Boldrini; F A Champagne; V Arango; J J Mann; C A Stockmeier; H Galfalvy; P R Albert; K J Ressler; R Hen
Journal:  Transl Psychiatry       Date:  2016-03-01       Impact factor: 6.222

Review 9.  HTR1A Polymorphisms and Clinical Efficacy of Antipsychotic Drug Treatment in Schizophrenia: A Meta-Analysis.

Authors:  Yoshiteru Takekita; Chiara Fabbri; Masaki Kato; Yosuke Koshikawa; Aran Tajika; Toshihiko Kinoshita; Alessandro Serretti
Journal:  Int J Neuropsychopharmacol       Date:  2016-04-29       Impact factor: 5.176

10.  Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

Authors:  S Stringer; C C Minică; K J H Verweij; H Mbarek; M Bernard; J Derringer; K R van Eijk; J D Isen; A Loukola; D F Maciejewski; E Mihailov; P J van der Most; C Sánchez-Mora; L Roos; R Sherva; R Walters; J J Ware; A Abdellaoui; T B Bigdeli; S J T Branje; S A Brown; M Bruinenberg; M Casas; T Esko; I Garcia-Martinez; S D Gordon; J M Harris; C A Hartman; A K Henders; A C Heath; I B Hickie; M Hickman; C J Hopfer; J J Hottenga; A C Huizink; D E Irons; R S Kahn; T Korhonen; H R Kranzler; K Krauter; P A C van Lier; G H Lubke; P A F Madden; R Mägi; M K McGue; S E Medland; W H J Meeus; M B Miller; G W Montgomery; M G Nivard; I M Nolte; A J Oldehinkel; Z Pausova; B Qaiser; L Quaye; J A Ramos-Quiroga; V Richarte; R J Rose; J Shin; M C Stallings; A I Stiby; T L Wall; M J Wright; H M Koot; T Paus; J K Hewitt; M Ribasés; J Kaprio; M P Boks; H Snieder; T Spector; M R Munafò; A Metspalu; J Gelernter; D I Boomsma; W G Iacono; N G Martin; N A Gillespie; E M Derks; J M Vink
Journal:  Transl Psychiatry       Date:  2016-03-29       Impact factor: 6.222
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  119 in total

1.  An integrative systems-based analysis of substance use: eQTL-informed gene-based tests, gene networks, and biological mechanisms.

Authors:  Zachary F Gerring; Angela Mina Vargas; Eric R Gamazon; Eske M Derks
Journal:  Am J Med Genet B Neuropsychiatr Genet       Date:  2020-12-23       Impact factor: 3.568

Review 2.  Neural substrates underlying the negative impact of cannabinoid exposure during adolescence.

Authors:  Hanna M Molla; Kuei Y Tseng
Journal:  Pharmacol Biochem Behav       Date:  2020-06-09       Impact factor: 3.533

3.  Cannabis legalization: Did we make a mistake? Update 2019

Authors:  Marco Leyton
Journal:  J Psychiatry Neurosci       Date:  2019-09-01       Impact factor: 6.186

Review 4.  Cannabis use and cannabis use disorder.

Authors:  Jason P Connor; Daniel Stjepanović; Bernard Le Foll; Eva Hoch; Alan J Budney; Wayne D Hall
Journal:  Nat Rev Dis Primers       Date:  2021-02-25       Impact factor: 52.329

5.  Genetic Variants Associated With Anxiety and Stress-Related Disorders: A Genome-Wide Association Study and Mouse-Model Study.

Authors:  Sandra M Meier; Kalevi Trontti; Kirstin L Purves; Thomas Damm Als; Jakob Grove; Mikaela Laine; Marianne Giørtz Pedersen; Jonas Bybjerg-Grauholm; Marie Bækved-Hansen; Ewa Sokolowska; Preben B Mortensen; David M Hougaard; Thomas Werge; Merete Nordentoft; Gerome Breen; Anders D Børglum; Thalia C Eley; Iiris Hovatta; Manuel Mattheisen; Ole Mors
Journal:  JAMA Psychiatry       Date:  2019-09-01       Impact factor: 21.596

6.  Onset of regular cannabis use and adult sleep duration: Genetic variation and the implications of a predictive relationship.

Authors:  Evan A Winiger; Spencer B Huggett; Alexander S Hatoum; Michael C Stallings; John K Hewitt
Journal:  Drug Alcohol Depend       Date:  2019-08-30       Impact factor: 4.492

7.  Ranking evidence in substance use and addiction.

Authors:  Hudson Reddon; Thomas Kerr; M-J Milloy
Journal:  Int J Drug Policy       Date:  2020-07-06

8.  Identification of Functional Genetic Variants Associated With Alcohol Dependence and Related Phenotypes Using a High-Throughput Assay.

Authors:  Kriti S Thapa; Andy B Chen; Dongbing Lai; Xiaoling Xuei; Leah Wetherill; Jay A Tischfield; Yunlong Liu; Howard J Edenberg
Journal:  Alcohol Clin Exp Res       Date:  2020-11-17       Impact factor: 3.455

9.  Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies.

Authors:  Suhas Ganesh; Jose Cortes-Briones; Mohini Ranganathan; Rajiv Radhakrishnan; Patrick D Skosnik; Deepak Cyril D'Souza
Journal:  Int J Neuropsychopharmacol       Date:  2020-12-03       Impact factor: 5.176

Review 10.  Recent Efforts to Dissect the Genetic Basis of Alcohol Use and Abuse.

Authors:  Sandra Sanchez-Roige; Abraham A Palmer; Toni-Kim Clarke
Journal:  Biol Psychiatry       Date:  2019-09-25       Impact factor: 13.382
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