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PMID |
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TITLE |
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Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. |
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ABSTRACT |
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To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10 ). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10 ). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10 ), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10 ) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10 ). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10 ; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10 ). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10 ; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2019/09/10 |
accepted |
2020/01/30 |
revised |
2020/01/15 |
entrez |
2020/02/27 06:00 |
pubmed |
2020/02/27 06:00 |
medline |
2020/02/27 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Polimanti R |
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Polimanti |
Renato |
R |
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Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA. |
Walters RK |
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Walters |
Raymond K |
RK |
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Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. |
Johnson EC |
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Johnson |
Emma C |
EC |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
McClintick JN |
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McClintick |
Jeanette N |
JN |
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Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. |
Adkins AE |
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Adkins |
Amy E |
AE |
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Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA. |
Adkins DE |
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Adkins |
Daniel E |
DE |
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Department of Psychiatry, University of Utah, Salt Lake City, UT, USA. |
Bacanu SA |
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Bacanu |
Silviu-Alin |
SA |
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Virginia Commonwealth University Alcohol Research Center, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA. |
Bierut LJ |
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Bierut |
Laura J |
LJ |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Bigdeli TB |
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Bigdeli |
Tim B |
TB |
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Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA. |
Brown S |
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Brown |
Sandra |
S |
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Department of Psychiatry, University of California San Diego, San Diego, CA, USA. |
Bucholz KK |
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Bucholz |
Kathleen K |
KK |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Copeland WE |
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Copeland |
William E |
WE |
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Department of Psychiatry, University of Vermont Medical Center, Burlington, VT, USA. |
Costello EJ |
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Costello |
E Jane |
EJ |
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Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. |
Degenhardt L |
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Degenhardt |
Louisa |
L |
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National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia. |
Farrer LA |
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Farrer |
Lindsay A |
LA |
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Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA. |
Foroud TM |
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Foroud |
Tatiana M |
TM |
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. |
Fox L |
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Fox |
Louis |
L |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Goate AM |
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Goate |
Alison M |
AM |
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Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. |
Grucza R |
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Grucza |
Richard |
R |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Hack LM |
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Hack |
Laura M |
LM |
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Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. |
Hancock DB |
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Hancock |
Dana B |
DB |
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Center for Omics Discovery and Epidemiology, RTI International, Research Triangle Park, NC, USA. |
Hartz SM |
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Hartz |
Sarah M |
SM |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Heath AC |
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Heath |
Andrew C |
AC |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Hewitt JK |
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Hewitt |
John K |
JK |
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Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA. |
Hopfer CJ |
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Hopfer |
Christian J |
CJ |
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Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA. |
Johnson EO |
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Johnson |
Eric O |
EO |
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Center for Omics Discovery and Epidemiology, RTI International, Research Triangle Park, NC, USA. |
Kendler KS |
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Kendler |
Kenneth S |
KS |
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Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. |
Kranzler HR |
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Kranzler |
Henry R |
HR |
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Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine, VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA. |
Krauter K |
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Krauter |
Kenneth |
K |
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Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA. |
Lai D |
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Lai |
Dongbing |
D |
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. |
Madden PAF |
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Madden |
Pamela A F |
PAF |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
Maes HH |
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Maes |
Hermine H |
HH |
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Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. |
Nelson EC |
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Nelson |
Elliot C |
EC |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Peterson RE |
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Peterson |
Roseann E |
RE |
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Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. |
Porjesz B |
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Porjesz |
Bernice |
B |
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Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA. |
Riley BP |
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Riley |
Brien P |
BP |
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Virginia Commonwealth University Alcohol Research Center, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA. |
Saccone N |
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Saccone |
Nancy |
N |
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Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA. |
Stallings M |
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Stallings |
Michael |
M |
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Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA. |
Wall TL |
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Wall |
Tamara L |
TL |
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Department of Psychiatry, University of California San Diego, San Diego, CA, USA. |
Webb BT |
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Webb |
Bradley T |
BT |
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Virginia Commonwealth University Alcohol Research Center, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA. |
Wetherill L |
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Wetherill |
Leah |
L |
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. |
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Psychiatric Genomics Consortium Substance Use Disorders Workgroup |
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Edenberg HJ |
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Edenberg |
Howard J |
HJ |
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Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. |
Agrawal A |
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Agrawal |
Arpana |
A |
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Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. |
Gelernter J |
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Gelernter |
Joel |
J |
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Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA. joel.gelernter@yale.edu. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: |
ISSUE: |
TITLE: Molecular psychiatry |
ISOABBREVIATION: Mol. Psychiatry |
YEAR: 2020 |
MONTH: Feb |
DAY: 26 |
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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COMMENTS AND CORRECTIONS |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
R01 DA012690 |
NIDA NIH HHS |
United States |
R21 DA047527 |
NIDA NIH HHS |
United States |
U01 MH109532 |
NIMH NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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SUPPLEMENTARY MESH |
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OTHER ID's |
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