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Behavior Genetics

, Volume 46, Issue 2, pp 151–169 | Cite as

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

  • Tae-Hwi Schwantes-An
  • Juan Zhang
  • Li-Shiun Chen
  • Sarah M. Hartz
  • Robert C. Culverhouse
  • Xiangning Chen
  • Hilary Coon
  • Josef Frank
  • Helen M. Kamens
  • Bettina Konte
  • Leena Kovanen
  • Antti Latvala
  • Lisa N. Legrand
  • Brion S. Maher
  • Whitney E. Melroy
  • Elliot C. Nelson
  • Mark W. Reid
  • Jason D. Robinson
  • Pei-Hong Shen
  • Bao-Zhu Yang
  • Judy A. Andrews
  • Paul Aveyard
  • Olga Beltcheva
  • Sandra A. Brown
  • Dale S. Cannon
  • Sven Cichon
  • Robin P. Corley
  • Norbert Dahmen
  • Louisa Degenhardt
  • Tatiana Foroud
  • Wolfgang Gaebel
  • Ina Giegling
  • Stephen J. Glatt
  • Richard A. Grucza
  • Jill Hardin
  • Annette M. Hartmann
  • Andrew C. Heath
  • Stefan Herms
  • Colin A. Hodgkinson
  • Per Hoffmann
  • Hyman Hops
  • David Huizinga
  • Marcus Ising
  • Eric O. Johnson
  • Elaine Johnstone
  • Radka P. Kaneva
  • Kenneth S. Kendler
  • Falk Kiefer
  • Henry R. Kranzler
  • Ken S. Krauter
  • Orna Levran
  • Susanne Lucae
  • Michael T. Lynskey
  • Wolfgang Maier
  • Karl Mann
  • Nicholas G. Martin
  • Manuel Mattheisen
  • Grant W. Montgomery
  • Bertram Müller-Myhsok
  • Michael F. Murphy
  • Michael C. Neale
  • Momchil A. Nikolov
  • Denise Nishita
  • Markus M. Nöthen
  • John Nurnberger
  • Timo Partonen
  • Michele L. Pergadia
  • Maureen Reynolds
  • Monika Ridinger
  • Richard J. Rose
  • Noora Rouvinen-Lagerström
  • Norbert Scherbaum
  • Christine Schmäl
  • Michael Soyka
  • Michael C. Stallings
  • Michael Steffens
  • Jens Treutlein
  • Ming Tsuang
  • Tamara L. Wall
  • Norbert Wodarz
  • Vadim Yuferov
  • Peter Zill
  • Andrew W. Bergen
  • Jingchun Chen
  • Paul M. Cinciripini
  • Howard J. Edenberg
  • Marissa A. Ehringer
  • Robert E. Ferrell
  • Joel Gelernter
  • David Goldman
  • John K. Hewitt
  • Christian J. Hopfer
  • William G. Iacono
  • Jaakko Kaprio
  • Mary Jeanne Kreek
  • Ivo M. Kremensky
  • Pamela A.F. Madden
  • Matt McGue
  • Marcus R. Munafò
  • Robert A. Philibert
  • Marcella Rietschel
  • Alec Roy
  • Dan Rujescu
  • Sirkku T. Saarikoski
  • Gary E. Swan
  • Alexandre A. Todorov
  • Michael M. Vanyukov
  • Robert B. Weiss
  • Laura J. Bierut
  • Nancy L. Saccone
Original Research

Abstract

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for “general” substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95 % C.I. [0.83–0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.

Keywords

Addiction Substance dependence OPRM1 Opioid receptor Single nucleotide polymorphism (SNP) Genetic association 

Notes

Acknowledgments

For facilitating this collaboration to meta-analyze rs1799971, we thank Jonathan Pollock and the National Institute on Drug Abuse, which provided infrastructure support through conference calls and meetings. For this project we wish to acknowledge and thank the following people. For meta-analysis coordination at Washington University: Weimin Duan. For administrative support at Washington University: Sherri Fisher. We also thank Michael Bruchas, Washington University, for helpful discussions. For CADD: principal investigators John Hewitt, Institute for Behavioral Genetics, University of Colorado Boulder; Michael Stallings, Institute for Behavioral Genetics, University of Colorado Boulder; Christian Hopfer, University of Denver; Sandra Brown, University of California San Diego. For COGA: Principal Investigators B. Porjesz, V. Hesselbrock, H. Edenberg, L. Bierut; COGA includes ten different centers: University of Connecticut (V. Hesselbrock); Indiana University (H.J. Edenberg, J. Nurnberger Jr., T. Foroud); University of Iowa (S. Kuperman, J. Kramer); SUNY Downstate (B. Porjesz); Washington University in St. Louis (L. Bierut, A. Goate, J. Rice, K. Bucholz); University of California at San Diego (M. Schuckit); Rutgers University (J. Tischfield); Texas Biomedical Research Institute (L. Almasy), Howard University (R. Taylor) and Virginia Commonwealth University (D. Dick). Other COGA collaborators include: L. Bauer (University of Connecticut); D. Koller, S. O’Connor, L. Wetherill, X. Xuei (Indiana University); Grace Chan (University of Iowa); S. Kang, N. Manz, M. Rangaswamy (SUNY Downstate); J. Rohrbaugh, J-C Wang (Washington University in St. Louis); A. Brooks (Rutgers University); and F. Aliev (Virginia Commonwealth University). A. Parsian and M. Reilly are the NIAAA Staff Collaborators. We continue to be inspired by our memories of Henri Begleiter and Theodore Reich, founding PI and Co-PI of COGA, and also owe a debt of gratitude to other past organizers of COGA, including Ting-Kai Li, currently a consultant with COGA, P. Michael Conneally, Raymond Crowe, and Wendy Reich, for their critical contributions. The authors thank Kim Doheny and Elizabeth Pugh from CIDR and Justin Paschall from the NCBI dbGaP staff for valuable assistance with genotyping and quality control in developing the dataset available at dbGaP. For COGEND: COGEND is a collaborative research group and a part of the NIDA Genetics Consortium. Michael Brent, Alison Goate, Dorothy Hatsukami, Anthony Hinrichs, Heidi Kromrei, Tracey Richmond, Joe Henry Steinbach, Jerry Stitzel, Scott Saccone, Sharon Murphy; in memory of Theodore Reich, founding Principal Investigator of COGEND, we are indebted to his leadership in the establishment and nurturing of COGEND and acknowledge with great admiration his seminal scientific contributions to the field. For GADD: John Hewitt, Institute for Behavioral Genetics, University of Colorado Boulder; Michael Stallings, Institute for Behavioral Genetics, University of Colorado Boulder; Christian Hopfer, University of Denver; Sandra Brown, University of California San Diego. For Kreek: Matthew Randesi. For NAG: Yi-Ling Chou. For Yale-Penn: Genotyping services for a part of Yale-Penn were provided by the Center for Inherited Disease Research (CIDR) and Yale University (Center for Genome Analysis).

Funding

R01 DA026911 from The National Institute on Drug Abuse (NIDA) supported this project and the coordinating team at Washington University. BG/ROMA are supported by R01 DA018823 (Todorov) from NIDA. CADD/GADD/NYS are supported by R01 DA021905 (Brown, Wall), R01 AA017889 (Ehringer), P60 DA011015 (Hewitt), R01 DA012845 (Hewitt), T32 DA017637 (Hewitt), R01 DA021913 (Hopfer), K24 DA032555 (Hopfer), K01 AA019447 (Kamens), and R01 DA035804 (Wall, Hopfer, Stallings) from NIDA and NIAAA. CATS is supported by R01 DA017305 (Nelson) from NIDA. Dr. Degenhardt is supported by an Australian National Health and Medical Research Council (NHMRC) principal research fellowship (#1041472). The National Drug and Alcohol Research Centre at UNSW Australia is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund. CEDAR-SADS is supported by R01 DA019157 (Vanyukov) from NIDA. CEDAR is supported by P50 DA005605 (Tarter) from NIDA. SADS is supported by R01 DA011922 (Vanyukov) from NIDA. The following studies made up the Cinciripini study: CASSI is supported by R01 DA11822 (Cinciripini), PEERS EMA is supported by K07 CA92209 (Carter), PEERS NS is supported by R21 CA81649 (Cinciripini) and PEERS WS, PEERS NS and SCOPE are supported by P50 CA070907 (Cinciripini) from NIDA and NCI. COGA is supported by U10 AA008401 (Bierut, Nurnberger, Edenberg, Hesselbrock, Porjesz) from NIAAA and genotyping was supported by U01 HG004438 (Valle) from The Genes and Environment Initiative (GEI) and HHSN268200782096C from the National Institutes of Health (NIH). Contributions from COGEND are supported by R01 DA019963 (Bierut), R01 DA013423 (Bierut), P01 CA089392 (Bierut), K08 DA030398 (L.-S. Chen), K08 DA032680 (Hartz), R01 DA019963 (Bierut), R01 DA038076 (L.-S. Chen), R21 DA038241 (Culverhouse), R01 DA026911 (Saccone) and R01 DA036583 (Bierut) from NIDA and the National Cancer Institute (NCI). Funding for COGEND genotyping was provided by 1 X01 HG005274-01 and performed at Center for Inherited Disease Research (CIDR) which is funded through a federal contract from NIH to JHU (HHSN268200782096C). Finnish Health 2000 is supported by Finnish National Institute for Health and Welfare institutional funding. FSCD is supported by R01 DA013423 (Bierut) from NIDA. Gene Environment Association Studies (GENEVA) Coordinating Center assisted with genotype cleaning as well as general study coordination, for FSCD; GENEVA is supported by U01 HG004446. FTC/FT12 is supported by K02 AA018755 (Rose), R01 AA-09203 (Rose), R37 AA-12502 (Rose), 141054 (Kaprio) and 263278 (Kaprio) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and Academy of Finland. FTC/NAG-FIN is funded by GRAND (Kaprio) from Pfizer Inc., 213506 (Kaprio) and 129680 (Kaprio) from Academy of Finland, Health-F4-2007-201413 (Kaprio) from European Union Seventh Framework Programme, ENGAGE project, DA12854 (Madden) from NIDA, Wellcome Trust Sanger Institute, Sigrid Juselius Foundation and Jenny & Antti Wihuri Foundation. GESGA is supported by 01EB0410 (Mann), 01GS0852 (Kiefer), and  BMBF 01ZX1311A (Kiefer, Rietschel) (e:Med program) from the German Federal Ministry of Education and Research (BMBF), FZK 01GS08152 (Nöthen, Rietschel) from National Genome Research Network (NGFN Plus). Drs. Cichon and Nöthen are supported by Alfried Krupp von Bohlen und Halbach-Stiftung. IAS is supported by R01 DA015789 (Philibert) from NIDA. Kreek is supported by P50 DA05130 (Kreek) from NIDA and The Adelson Medical Research Foundation (Kreek). MCTFR is supported by R01 DA005147 (Iacono), R01 DA036216 (Iacono) and R01 U01 DA024417 (Iacono) from NIDA, R01 AA009367 (McGue) and R01 AA0011886 (McGue) from NIAAA and R01 MH066140 (McGue) from the National Institute of Mental Health (NIMH). MGHD is supported by R01 DA012846 (Tsuang) from NIDA and grants from NARSAD: The Brain and Behavior Research Foundation (Tsuang, Glatt), the Sidney R. Baer, Jr. Foundation (Tsuang), and the Gerber Foundation (Glatt). OYSUP is supported by RC2 DA028793 (Andrews) from NIDA. OZALC-NAG is supported by R01 AA075356 (Heath), R01 AA07728 (Heath), R01 AA13220 (Martin), R01 AA13321 (Heath), R01 AA13322 (Heath), R01 AA11998 (Heath) and R01 AA17688 (Heath) from NIAAA, R01 DA12854 (Madden) and K08 DA019951 (Pergadia) from NIDA and grants from the Australian National Health and Medical Research Council. Patch II/PiP are supported by C53/A6281 (Aveyard) from Cancer Research UK. Marcus Munafò and Paul Aveyard are members of the United Kingdom Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research: Centre of Excellence. Funding from British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. SMOFAM is supported by R01 DA003706 (Hops), U01 DA020830 (Lerman) from NIDA and 7PT2000-2004 (Swan) from University of California Tobacco-Related Disease Research Program. Utah is supported by P01 HL72903 (Hoidal) from NIDA and NHLBI. VA-Twin is supported by DA019498 (X. Chen) from NIDA; support was also provided by R01 DA18673 (Neale) from NIDA. Yale-Penn is supported by RC2 DA028909 (Gelernter), R01 DA12690 (Gelernter), R01 DA12849 (Gelernter), R01 DA18432 (Kranzler) and K01 DA24758 (Yang) from NIDA, R01 AA017535 (Gelernter) and R01 AA11330 (Gelernter) from NIAAA and Dr. Yang is supported by a Young Investigator Award from NARSAD: the Brain and Behavior Research Fund. Dr. Schwantes-An is also supported by the Division of Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Funding sources had no further role in the study design; in the collection, analysis and interpretation of data; in the writing; or in the decision to submit the paper for publication.

Compliance with Ethical Standards

Conflict of interest

Dr. Bierut is listed as an inventor on Issued U.S. Patent 8 080 371, “Markers for Addiction” covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction, and served as a consultant for Pfizer in 2008. Dr. NL Saccone is the spouse of Dr. SF Saccone, who is also listed as an inventor on the above patent. Dr. Cinciripini served on the scientific advisory board of Pfizer, conducted educational talks sponsored by Pfizer on smoking cessation (2006–2008), and has received grant support from Pfizer. Dr. Degenhardt has no relevant disclosures for this specific project; however, for general pharmaceutical company disclosures, Dr. Degenhardt has received untied educational grants from Reckitt Benckiser to conduct post-marketing surveillance of the diversion and injection of opioid substitution therapy medications in Australia. Although these activities are unrelated to the current study, Dr. Kranzler has been a consultant or advisory board member for Alkermes, Lilly, Lundbeck, Otsuka and Pfizer; he is also a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which is supported by Ethypharm, Lilly, Lundbeck, AbbVie, and Pfizer. Dr. Ridinger is member of the advisory board of Lundbeck referring to Nalmefene. Prof. Dr. N. Scherbaum received honoraria for several activities (advisory boards, lectures, manuscripts and educational material) by the factories Sanofi-Aventis, Reckitt-Benckiser, Lundbeck, and Janssen-Cilag. During the last three years he participated in clinical trials financed by the pharmaceutical industry. The remaining authors declare no conflict of interest.

Informed Consent

The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. All participants provided informed consent.

Supplementary material

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Supplementary material 1 (DOCX 187 kb)
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Supplementary material 2 (DOCX 30 kb)
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Supplementary material 3 (DOCX 524 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Tae-Hwi Schwantes-An
    • 1
    • 2
  • Juan Zhang
    • 1
    • 69
  • Li-Shiun Chen
    • 3
  • Sarah M. Hartz
    • 3
  • Robert C. Culverhouse
    • 4
  • Xiangning Chen
    • 5
  • Hilary Coon
    • 6
  • Josef Frank
    • 7
  • Helen M. Kamens
    • 8
    • 9
    • 10
  • Bettina Konte
    • 11
  • Leena Kovanen
    • 12
  • Antti Latvala
    • 13
  • Lisa N. Legrand
    • 14
  • Brion S. Maher
    • 15
  • Whitney E. Melroy
    • 8
    • 9
  • Elliot C. Nelson
    • 3
  • Mark W. Reid
    • 16
  • Jason D. Robinson
    • 17
  • Pei-Hong Shen
    • 18
  • Bao-Zhu Yang
    • 19
  • Judy A. Andrews
    • 16
  • Paul Aveyard
    • 20
  • Olga Beltcheva
    • 21
  • Sandra A. Brown
    • 22
  • Dale S. Cannon
    • 6
  • Sven Cichon
    • 23
    • 24
  • Robin P. Corley
    • 8
  • Norbert Dahmen
    • 25
  • Louisa Degenhardt
    • 26
    • 27
  • Tatiana Foroud
    • 28
  • Wolfgang Gaebel
    • 29
  • Ina Giegling
    • 11
  • Stephen J. Glatt
    • 30
  • Richard A. Grucza
    • 3
  • Jill Hardin
    • 31
  • Annette M. Hartmann
    • 11
  • Andrew C. Heath
    • 3
  • Stefan Herms
    • 23
    • 24
  • Colin A. Hodgkinson
    • 18
  • Per Hoffmann
    • 23
    • 24
  • Hyman Hops
    • 16
  • David Huizinga
    • 33
  • Marcus Ising
    • 34
  • Eric O. Johnson
    • 35
  • Elaine Johnstone
    • 36
  • Radka P. Kaneva
    • 21
  • Kenneth S. Kendler
    • 5
  • Falk Kiefer
    • 37
  • Henry R. Kranzler
    • 38
  • Ken S. Krauter
    • 8
    • 39
  • Orna Levran
    • 40
  • Susanne Lucae
    • 34
  • Michael T. Lynskey
    • 41
  • Wolfgang Maier
    • 32
  • Karl Mann
    • 42
  • Nicholas G. Martin
    • 43
  • Manuel Mattheisen
    • 23
    • 44
    • 45
  • Grant W. Montgomery
    • 43
  • Bertram Müller-Myhsok
    • 34
  • Michael F. Murphy
    • 46
  • Michael C. Neale
    • 5
  • Momchil A. Nikolov
    • 3
    • 21
  • Denise Nishita
    • 31
  • Markus M. Nöthen
    • 23
  • John Nurnberger
    • 47
  • Timo Partonen
    • 12
  • Michele L. Pergadia
    • 3
  • Maureen Reynolds
    • 48
  • Monika Ridinger
    • 49
    • 67
  • Richard J. Rose
    • 50
  • Noora Rouvinen-Lagerström
    • 12
  • Norbert Scherbaum
    • 51
  • Christine Schmäl
    • 42
  • Michael Soyka
    • 52
    • 53
  • Michael C. Stallings
    • 8
    • 54
  • Michael Steffens
    • 55
  • Jens Treutlein
    • 7
  • Ming Tsuang
    • 22
  • Tamara L. Wall
    • 22
  • Norbert Wodarz
    • 49
  • Vadim Yuferov
    • 40
  • Peter Zill
    • 56
  • Andrew W. Bergen
    • 31
  • Jingchun Chen
    • 5
  • Paul M. Cinciripini
    • 17
  • Howard J. Edenberg
    • 57
  • Marissa A. Ehringer
    • 8
    • 9
  • Robert E. Ferrell
    • 58
  • Joel Gelernter
    • 19
    • 59
    • 60
  • David Goldman
    • 18
  • John K. Hewitt
    • 8
    • 54
  • Christian J. Hopfer
    • 61
  • William G. Iacono
    • 14
  • Jaakko Kaprio
    • 12
    • 13
    • 62
  • Mary Jeanne Kreek
    • 40
  • Ivo M. Kremensky
    • 21
  • Pamela A.F. Madden
    • 3
  • Matt McGue
    • 14
  • Marcus R. Munafò
    • 63
  • Robert A. Philibert
    • 64
  • Marcella Rietschel
    • 7
  • Alec Roy
    • 65
  • Dan Rujescu
    • 11
  • Sirkku T. Saarikoski
    • 12
  • Gary E. Swan
    • 68
  • Alexandre A. Todorov
    • 3
  • Michael M. Vanyukov
    • 48
  • Robert B. Weiss
    • 66
  • Laura J. Bierut
    • 3
  • Nancy L. Saccone
    • 1
  1. 1.Department of GeneticsWashington University School of MedicineSt. LouisUSA
  2. 2.Genometrics Section, Computational and Statistical Genomics Branch, Division of Intramural Research, National Human Genome Research InstituteUS National Institutes of Health (NIH)BaltimoreUSA
  3. 3.Department of PsychiatryWashington University School of MedicineSt. LouisUSA
  4. 4.Department of Internal MedicineWashington University School of MedicineSt. LouisUSA
  5. 5.Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth UniversityRichmondUSA
  6. 6.Department of PsychiatryUniversity of Utah School of MedicineSalt Lake CityUSA
  7. 7.Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental HealthHeidelberg UniversityMannheimGermany
  8. 8.Institute for Behavioral GeneticsUniversity of ColoradoBoulderUSA
  9. 9.Department of Integrative PhysiologyUniversity of ColoradoBoulderUSA
  10. 10.Department of Biobehavioral HealthThe Pennsylvania State UniversityUniversity ParkUSA
  11. 11.Department of PsychiatryUniversitätsklinikum Halle (Saale)Halle (Saale)Germany
  12. 12.Department of Mental Health and Substance Abuse ServicesNational Institute for Health and WelfareHelsinkiFinland
  13. 13.Department of Public HealthUniversity of HelsinkiHelsinkiFinland
  14. 14.Department of PsychologyUniversity of MinnesotaMinneapolisUSA
  15. 15.Department of Mental Health, Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA
  16. 16.Oregon Research InstituteEugeneUSA
  17. 17.Department of Behavioral ScienceThe University of Texas MD Anderson Cancer CenterHoustonUSA
  18. 18.Section of Human NeurogeneticsNational Institute on Alcohol Abuse and AlcoholismBethesdaUSA
  19. 19.Department of PsychiatryYale UniversityNew HavenUSA
  20. 20.Department of Primary Care Health SciencesUniversity of OxfordOxfordUnited Kingdom
  21. 21.Department of Medical Chemistry and Biochemistry, Molecular Medicine CenterMedical University-SofiaSofiaBulgaria
  22. 22.Department of PsychiatryUniversity of California San DiegoLa JollaUSA
  23. 23.Department. of Genomics, Life and Brain Center, Institute of Human GeneticsUniversity of BonnBonnGermany
  24. 24.Division of Medical Genetics, Department of BiomedicineUniversity Hospital Basel, University of BaselBaselSwitzerland
  25. 25. Ökumenisches Hainich-KlinikumMühlhausen/ThüringenGermany
  26. 26.National Drug and Alcohol Research CentreUniversity of New South WalesRandwickAustralia
  27. 27.School of Population and Global HealthUniversity of MelbourneMelbourneAustralia
  28. 28.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA
  29. 29.University of DüsseldorfDüsseldorfGermany
  30. 30.Department of Psychiatry and Behavioral SciencesSUNY Upstate Medical UniversitySyracuseUSA
  31. 31.Center for Health Sciences, Biosciences DivisionSRI InternationalMenlo ParkUSA
  32. 32.University of BonnBonnGermany
  33. 33.Institute of Behavioral ScienceUniversity of ColoradoBoulderUSA
  34. 34.Max-Planck-Institute of PsychiatryMunichGermany
  35. 35.Behavioral Health Research DivisionResearch Triangle Institute InternationalDurhamUSA
  36. 36.Department of OncologyUniversity of OxfordOxfordUnited Kingdom
  37. 37.Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental HealthHeidelberg UniversityMannheimGermany
  38. 38.Department of Psychiatry, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  39. 39.Molecular, Cellular, and Developmental BiologyUniversity of ColoradoBoulderUSA
  40. 40.Laboratory of the Biology of Addictive DiseasesThe Rockefeller UniversityNew YorkUSA
  41. 41.Addictions Department, Institute of PsychiatryKing’s College LondonLondonUK
  42. 42.Medical Faculty Mannheim, Central Institute of Mental HealthHeidelberg UniversityMannheimGermany
  43. 43.Department of Genetic EpidemiologyQueensland Institute of Medical ResearchBrisbaneAustralia
  44. 44.Harvard School of Public HealthBostonUSA
  45. 45.Aarhus UniversityAarhusDenmark
  46. 46.Childhood Cancer Research GroupUniversity of OxfordOxfordUK
  47. 47.Department of PsychiatryIndiana University School of MedicineIndianapolisUSA
  48. 48.Department of Pharmaceutical SciencesUniversity of PittsburghPittsburghUSA
  49. 49.Department of PsychiatryUniversity Medical Center Regensburg, University of RegensburgRegensburgGermany
  50. 50.Department of Psychological and Brain SciencesIndiana UniversityBloomingtonUSA
  51. 51.Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital EssenUniversity of Duisburg-EssenEssenGermany
  52. 52.Department of PsychiatryUniversity of MunichMunichGermany
  53. 53.Private Hospital MeiringenMeiringenSwitzerland
  54. 54.Department of Psychology & NeuroscienceUniversity of ColoradoBoulderUSA
  55. 55.Research DepartmentFederal Institute for Drugs and Medical Devices (BfArM)BonnGermany
  56. 56.University of MunichMunichGermany
  57. 57.Department of Biochemistry and Molecular BiologyIndiana University School of MedicineIndianapolisUSA
  58. 58.Department of Human GeneticsUniversity of PittsburghPittsburghUSA
  59. 59.Department of GeneticsYale UniversityNew HavenUSA
  60. 60.Department of NeurobiologyYale UniversityNew HavenUSA
  61. 61.Department of PsychiatryUniversity of Colorado Anschutz Medical CampusAuroraUSA
  62. 62.Institute for Molecular Medicine FIMMUniversity of HelsinkiHelsinkiFinland
  63. 63.MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental PsychologyUniversity of BristolBristolUK
  64. 64.Department of PsychiatryUniversity of IowaIowa CityUSA
  65. 65.Psychiatry Service, Department of Veteran AffairsNew Jersey VA Health Care SystemEast OrangeUSA
  66. 66.Department of Human GeneticsUniversity of Utah School of MedicineSalt Lake CityUSA
  67. 67.Psychiatric Hospital, KonigsfeldenWindischSwitzerland
  68. 68.Department of Medicine, Stanford Prevention Research CenterStanford University School of MedicineStanfordUSA
  69. 69.Key Laboratory of Brain Function and Disease, School of Life Sciences, Chinese Academy of SciencesUniversity of Science and Technology of ChinaHefeiChina

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