Evidence map›Paper›PMID 26239289›Full record

SynthesisMolecular psychiatry2016

Evidence of CNIH3 involvement in opioid dependence.

E C Nelson, A Agrawal, A C Heath, R Bogdan, R Sherva, B Zhang, R Al-Hasani, M R Bruchas, Y-L Chou, C H Demers and 29 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 7 pooled it
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 7 syntheses or guidelines pooled it, 143 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. Article
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  11. Review
  12. Article
  13. Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025
    Review
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  15. Article
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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors at 17 institutions in 3 countries.

E C NelsonDepartment of Psychiatry, Washington University, St Louis, MO, USA.
A AgrawalDepartment of Psychiatry, Washington University, St Louis, MO, USA.
A C HeathDepartment of Psychiatry, Washington University, St Louis, MO, USA.
R BogdanDepartment of Psychiatry, Washington University, St Louis, MO, USA.
R ShervaBoston University School of Medicine, Boston, MA, USA.
B ZhangDepartment of Psychiatry, Washington University, St Louis, MO, USA.
R Al-HasaniDepartment of Psychiatry, Washington University, St Louis, MO, USA.
M R BruchasDepartment of Psychiatry, Washington University, St Louis, MO, USA.
Y-L ChouDepartment of Psychiatry, Washington University, St Louis, MO, USA.
C H DemersDepartment of Psychiatry, Washington University, St Louis, MO, USA.
C E CareyDepartment of Psychiatry, Washington University, St Louis, MO, USA.
E D Conley23andMe, Mountain View, CA, USA.
A K FakiraColumbia University College of Physicians and Surgeons, New York, NY, USA.
L A FarrerBoston University School of Medicine, Boston, MA, USA.
A GoateIcahn School of Medicine at Mount Sinai, New York, NY, USA.
S GordonQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
A K HendersQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
V HesselbrockUniversity of Connecticut School of Medicine, Farmington, CT, USA.
M KapoorIcahn School of Medicine at Mount Sinai, New York, NY, USA.
M T LynskeyInstitute of Psychiatry, King's College, London, UK.
P A F MaddenDepartment of Psychiatry, Washington University, St Louis, MO, USA.
J A MoronColumbia University College of Physicians and Surgeons, New York, NY, USA.
J P RiceDepartment of Psychiatry, Washington University, St Louis, MO, USA.
N L SacconeDepartment of Psychiatry, Washington University, St Louis, MO, USA.
S G SchwabFaculty of Science Medicine & Health, University of Wollongong, Wollongong, Australia.
F L ShandBlack Dog Institute, Sydney, Australia.
A A TodorovDepartment of Psychiatry, Washington University, St Louis, MO, USA.
L WallaceQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
T WangDepartment of Psychiatry, Washington University, St Louis, MO, USA.
N R WrayThe University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.
X ZhouSt Jude Children's Research Hospital, Memphis, TN, USA.
L DegenhardtNational Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
N G MartinQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
A R HaririDuke University, Durham, NC, USA.
H R KranzlerUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
J GelernterYale School of Medicine, New Haven, CT, USA.
L J BierutDepartment of Psychiatry, Washington University, St Louis, MO, USA.
D J ClarkStanford University School of Medicine, Stanford, CA, USA.
G W MontgomeryQIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Washington University in St. Louis · USQIMR Berghofer Medical Research Institute · AUBoston University · USColumbia University · USIcahn School of Medicine at Mount Sinai · US23andMe (United States) · USBlack Dog Institute · AUDuke University · USKing's College London · GBStanford University · USSt. Jude Children's Research Hospital · USUniversity of Connecticut · USUniversity of Pennsylvania · USUniversity of Queensland · AUUniversity of Wollongong · AUUNSW Sydney · AUYale University · US

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JAY Arnold TISCHFIELD · 1989 to 2026
$162.7M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
Yale University Clinical and Translational Science Award ProgramUL1TR000142 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$31.8M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
Sex-specific analysis of opioid dependence GWAS and beyondR01DA012690 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2000 to 2017
$14.0M
GENETICS OF COCAINE DEPENDENCER01DA012849 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 1999 to 2010
$11.5M
Quantifying Individual Differences in Midlife Structural Brain Integrity Associated with Later AD/ADRD RiskR01AG049789 · NIA · DUKE UNIVERSITY · PI AHMAD R. HARIRI, TERRIE E MOFFITT · 2015 to 2026
$10.6M
Genome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6M
Linkage Disequilibrium Studies of Alcohol DependenceR01AA011330 · NIAAA · YALE UNIVERSITY · PI GELERNTER, JOEL · 1997 to 2013
$6.4M
RESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICSR25DA027995 · NIDA · WASHINGTON UNIVERSITY · PI MADDEN, PAMELA ANN, RICE, JOHN P. · 2009 to 2019
$4.3M
Genomewide Association Study of Cocaine Dependence in two PopulationsRC2DA028909 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2009 to 2010
$4.2M
BLRD VA I01 BX000881NCATS NIH HHS 8UL1TR000142-07NCATS NIH HHS UL1 TR000142NCI NIH HHS P01 CA089392NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS N01 HG065403NHGRI NIH HHS R01 HG007175NHGRI NIH HHS R01HG007175NHGRI NIH HHS R01 HG007354NHGRI NIH HHS R01HG007354NHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS HHSN268200782096CNIAAA NIH HHS R01 AA011330NIAAA NIH HHS R01 AA017535NIAAA NIH HHS R01 AA11330NIAAA NIH HHS U10 AA008401NIA NIH HHS R01 AG045231NIA NIH HHS R01-AG045231NIA NIH HHS R01 AG049789NIDA NIH HHS DA027995NIDA NIH HHS DA031579NIDA NIH HHS DA033369NIDA NIH HHS K02 DA032573NIDA NIH HHS K02DA32573NIDA NIH HHS K99 DA038725NIDA NIH HHS R01 DA012690NIDA NIH HHS R01 DA012849NIDA NIH HHS R01 DA013423NIDA NIH HHS R01 DA017305NIDA NIH HHS R01 DA018432NIDA NIH HHS R01 DA019963NIDA NIH HHS R01 DA023668NIDA NIH HHS R01 DA031579NIDA NIH HHS R01 DA033369NIDA NIH HHS R01DA12690NIDA NIH HHS R01 DA12849NIDA NIH HHS R01 DA17305NIDA NIH HHS R01 DA18432NIDA NIH HHS R01 DA23668NIDA NIH HHS R21 DA036826NIDA NIH HHS R25 DA027995NIDA NIH HHS RC2 DA028909NIDA NIH HHS T32 DA007313NIDA NIH HHS T32DA007313NIEHS NIH HHS R01 ES024992NIEHS NIH HHS R01ES024992NIGMS NIH HHS 5T32GM007205-38NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid-dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 single-nucleotide polymorphisms (SNPs), were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine and alcohol dependence and the Study of Addiction: Genetics and Environment, which both contain non-dependent opioid misusers and opioid-dependent individuals. Meta-analyses found five genome-wide significant CNIH3 SNPs. The A allele of rs10799590, the most highly associated SNP, was robustly protective (P=4.30E-9; odds ratio 0.64 (95% confidence interval 0.55-0.74)). Epigenetic annotation predicts that this SNP is functional in fetal brain. Neuroimaging data from the Duke Neurogenetics Study (N=312) provide evidence of this SNP's in vivo functionality; rs10799590 A allele carriers displayed significantly greater right amygdala habituation to threat-related facial expressions, a phenotype associated with resilience to psychopathology. Computational genetic analyses of physical dependence on morphine across 23 mouse strains yielded significant correlations for haplotypes in CNIH3 and functionally related genes. These convergent findings support CNIH3 involvement in the pathophysiology of opioid dependence, complementing prior studies implicating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate system.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideAmygdalaAnimalsFemaleGenome-Wide Association StudyHabituation, PsychophysiologicHumansMaleMembrane ProteinsMice, Inbred StrainsNerve Tissue ProteinsOpioid-Related DisordersReceptors, AMPASpecies SpecificityYoung AdultCnih2 protein, mouseCNIH3 protein, humanCNIH3 protein, mouseMembrane ProteinsNerve Tissue ProteinsReceptors, AMPA

Identifiers

PMID26239289
PMCPMC4740268
OpenAlexW1854766247

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.