Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
29112194
TITLE
Genome-wide association study identifies a novel locus for cannabis dependence.
ABSTRACT
Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.Molecular Psychiatry advance online publication, 7 November 2017; doi:10.1038/mp.2017.200.
DATE PUBLISHED
2017 Nov 07
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/10/10
revised 2017/06/26
accepted 2017/07/13
entrez 2017/11/08 06:00
pubmed 2017/11/08 06:00
medline 2017/11/08 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Agrawal A Agrawal A A Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Chou YL Chou Y-L YL Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Carey CE Carey C E CE Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA.
Baranger DAA Baranger D A A DAA Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA.
Zhang B Zhang B B Department of Developmental Biology, Washington University School of Medicine, St Louis, MO, USA.
Sherva R Sherva R R Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
Wetherill L Wetherill L L Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Kapoor M Kapoor M M Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Wang JC Wang J-C JC Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bertelsen S Bertelsen S S Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Anokhin AP Anokhin A P AP Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Hesselbrock V Hesselbrock V V Department of Psychiatry, University of Connecticut Health, Farmington, CT, USA.
Kramer J Kramer J J Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Lynskey MT Lynskey M T MT King's College London, Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, London, UK.
Meyers JL Meyers J L JL Downstate Medical Center, Department of Psychiatry, State University of New York, Brooklyn, NY, USA.
Nurnberger JI Nurnberger J I JI Stark Neuroscience Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Rice JP Rice J P JP Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Tischfield J Tischfield J J Rutgers, Department of Genetics, The State University of New Jersey, New Brunswick, NJ, USA.
Bierut LJ Bierut L J LJ Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Degenhardt L Degenhardt L L National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
Farrer LA Farrer L A LA Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
Gelernter J Gelernter J J US Department of Veterans Affairs, West Haven, CT, USA.
Hariri AR Hariri A R AR Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
Heath AC Heath A C AC Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Kranzler HR Kranzler H R HR Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
Madden PAF Madden P A F PAF Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Martin NG Martin N G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Montgomery GW Montgomery G W GW Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Porjesz B Porjesz B B Downstate Medical Center, Department of Psychiatry, State University of New York, Brooklyn, NY, USA.
Wang T Wang T T Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.
Whitfield JB Whitfield J B JB QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Edenberg HJ Edenberg H J HJ Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA.
Foroud T Foroud T T Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Goate AM Goate A M AM Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bogdan R Bogdan R R Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA.
Nelson EC Nelson E C EC Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2017
MONTH: Nov
DAY: 07
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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