Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
32099098
TITLE
Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.
ABSTRACT
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.
DATE PUBLISHED
2020 Feb 26
HISTORY
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
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Polimanti R Polimanti Renato R Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
Walters RK Walters Raymond K RK Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Johnson EC Johnson Emma C EC Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
McClintick JN McClintick Jeanette N JN Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Adkins AE Adkins Amy E AE Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
Adkins DE Adkins Daniel E DE Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
Bacanu SA Bacanu Silviu-Alin SA Virginia Commonwealth University Alcohol Research Center, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA.
Bierut LJ Bierut Laura J LJ Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Bigdeli TB Bigdeli Tim B TB Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
Brown S Brown Sandra S Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Bucholz KK Bucholz Kathleen K KK Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Copeland WE Copeland William E WE Department of Psychiatry, University of Vermont Medical Center, Burlington, VT, USA.
Costello EJ Costello E Jane EJ Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Degenhardt L Degenhardt Louisa L National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
Farrer LA Farrer Lindsay A LA Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
Foroud TM Foroud Tatiana M TM Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Fox L Fox Louis L Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Goate AM Goate Alison M AM Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Grucza R Grucza Richard R Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Hack LM Hack Laura M LM Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Hancock DB Hancock Dana B DB Center for Omics Discovery and Epidemiology, RTI International, Research Triangle Park, NC, USA.
Hartz SM Hartz Sarah M SM Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Hewitt JK Hewitt John K JK Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Hopfer CJ Hopfer Christian J CJ Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA.
Johnson EO Johnson Eric O EO Center for Omics Discovery and Epidemiology, RTI International, Research Triangle Park, NC, USA.
Kendler KS Kendler Kenneth S KS Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Kranzler HR Kranzler Henry R HR Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine, VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
Krauter K Krauter Kenneth K Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
Lai D Lai Dongbing D Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Madden PAF Madden Pamela A F PAF Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Maes HH Maes Hermine H HH Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Peterson RE Peterson Roseann E RE Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
Porjesz B Porjesz Bernice B Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
Riley BP Riley Brien P BP Virginia Commonwealth University Alcohol Research Center, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA.
Saccone N Saccone Nancy N Department of Genetics, Washington University School of Medicine, Saint Louis, MO, USA.
Stallings M Stallings Michael M Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Wall TL Wall Tamara L TL Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Webb BT Webb Bradley T BT Virginia Commonwealth University Alcohol Research Center, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA.
Wetherill L Wetherill Leah L Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Psychiatric Genomics Consortium Substance Use Disorders Workgroup
Edenberg HJ Edenberg Howard J HJ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Agrawal A Agrawal Arpana A Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA.
Gelernter J Gelernter Joel J Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA. joel.gelernter@yale.edu.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2020
MONTH: Feb
DAY: 26
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
COMMENTS AND CORRECTIONS
GRANTS
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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