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| PMID |
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| TITLE |
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| Genome-wide association study identifies a novel locus for cannabis dependence. |
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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| 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 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Agrawal A |
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Agrawal |
A |
A |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Chou YL |
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Chou |
Y-L |
YL |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Carey CE |
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Carey |
C E |
CE |
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Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA. |
| Baranger DAA |
|
Baranger |
D A A |
DAA |
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Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA. |
| Zhang B |
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Zhang |
B |
B |
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Department of Developmental Biology, Washington University School of Medicine, St Louis, MO, USA. |
| Sherva R |
|
Sherva |
R |
R |
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Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA. |
| Wetherill L |
|
Wetherill |
L |
L |
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. |
| Kapoor M |
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Kapoor |
M |
M |
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Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |
| Wang JC |
|
Wang |
J-C |
JC |
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Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |
| Bertelsen S |
|
Bertelsen |
S |
S |
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Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |
| Anokhin AP |
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Anokhin |
A P |
AP |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Hesselbrock V |
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Hesselbrock |
V |
V |
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Department of Psychiatry, University of Connecticut Health, Farmington, CT, USA. |
| Kramer J |
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Kramer |
J |
J |
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Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA. |
| Lynskey MT |
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Lynskey |
M T |
MT |
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King's College London, Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, London, UK. |
| Meyers JL |
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Meyers |
J L |
JL |
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Downstate Medical Center, Department of Psychiatry, State University of New York, Brooklyn, NY, USA. |
| Nurnberger JI |
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Nurnberger |
J I |
JI |
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Stark Neuroscience Center, Indiana University School of Medicine, Indianapolis, IN, USA. |
| Rice JP |
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Rice |
J P |
JP |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Tischfield J |
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Tischfield |
J |
J |
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Rutgers, Department of Genetics, The State University of New Jersey, New Brunswick, NJ, USA. |
| Bierut LJ |
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Bierut |
L J |
LJ |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Degenhardt L |
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Degenhardt |
L |
L |
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National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia. |
| Farrer LA |
|
Farrer |
L A |
LA |
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Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA. |
| Gelernter J |
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Gelernter |
J |
J |
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US Department of Veterans Affairs, West Haven, CT, USA. |
| Hariri AR |
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Hariri |
A R |
AR |
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Department of Psychology and Neuroscience, Duke University, Durham, NC, USA. |
| Heath AC |
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Heath |
A C |
AC |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Kranzler HR |
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Kranzler |
H R |
HR |
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Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA. |
| Madden PAF |
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Madden |
P A F |
PAF |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
| Martin NG |
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Martin |
N G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Montgomery GW |
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Montgomery |
G W |
GW |
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Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia. |
| Porjesz B |
|
Porjesz |
B |
B |
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Downstate Medical Center, Department of Psychiatry, State University of New York, Brooklyn, NY, USA. |
| Wang T |
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Wang |
T |
T |
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Department of Genetics, Washington University School of Medicine, St Louis, MO, USA. |
| Whitfield JB |
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Whitfield |
J B |
JB |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Edenberg HJ |
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Edenberg |
H J |
HJ |
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Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA. |
| Foroud T |
|
Foroud |
T |
T |
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. |
| Goate AM |
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Goate |
A M |
AM |
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Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |
| Bogdan R |
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Bogdan |
R |
R |
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Department of Psychological and Brain Sciences, Washington University in St. Louis, St Louis, MO, USA. |
| Nelson EC |
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Nelson |
E C |
EC |
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Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: Molecular psychiatry |
| ISOABBREVIATION: Mol. Psychiatry |
| YEAR: 2017 |
| MONTH: Nov |
| DAY: 07 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1476-5578 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Mol Psychiatry |
| COUNTRY: England |
| ISSNLINKING: 1359-4184 |
| NLMUNIQUEID: 9607835 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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