Evidence map›Paper›PMID 24143882›Full record

ArticleBiological psychiatry2014

Genome-wide association study of opioid dependence: multiple associations mapped to calcium and potassium pathways.

Joel Gelernter, Henry R Kranzler, Richard Sherva, Ryan Koesterer, Laura Almasy, Hongyu Zhao, Lindsay A Farrer

Abstract read
In one paragraph

Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 13 pooled it
10.8field-weighted citation impact, top 1% 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

160 citing papers in PubMed, 13 syntheses or guidelines pooled it, 250 citations in OpenAlex.

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  14. Article
  15. Assessing measurement bias in substance use disorder criteria associated with childhood adversity and genetic liability.Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors · 2026
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100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 7 institutions in 1 country.

Joel GelernterDepartment of Psychiatry, Division of Human Genetics, Departments of Genetics and Neurobiology, Yale University School of Medicine, VA Connecticut Healthcare Center, West Haven. Electronic address: joel.gelernter@yale.edu.
Henry R KranzlerPhiladelphia VA Medical Center, Philadelphia, Pennsylvania.
Richard ShervaDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts.
Ryan KoestererUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Laura AlmasyDepartment of Genetics, Texas Biomedical Research Institute, San Antonio, Texas.
Hongyu ZhaoDepartments Biostatistics and Genetics, Yale School of Public Health, Yale University, New Haven, CT.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts; Departments of Neurology, Ophthalmology, Genetics and Genomics, Epidemiology and Biostatistics, Boston University Schools of Medicine and Public Health, Boston, Massachusetts.
Boston Public Schools · USBoston University · USPhiladelphia VA Medical Center · USTexas Biomedical Research Institute · USUniversity of Pennsylvania · USVA Connecticut Healthcare System · USYale University · US

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JESSICA E SALVATORE · 1989 to 2026
$162.7M
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
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
Genomewide Association Study of Cocaine Dependence in two PopulationsRC2DA028909 · NIDA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2009 to 2010
$4.2M
Genetics of Cocaine DependenceR01DA018432 · NIDA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI KRANZLER, HENRY RICHARD · 2006 to 2010
$3.5M
Genetics of Alcohol Dependence in African-AmericansR01AA017535 · NIAAA · YALE UNIVERSITY · PI GELERNTER, JOEL · 2009 to 2013
$3.0M
FAMILY STUDY OF COCAINE DEPENDENCER01DA013423 · NIDA · WASHINGTON UNIVERSITY · PI BIERUT, LAURA JEAN · 2000 to 2004
$2.2M
NCATS NIH HHS UL1 TR000142NCI NIH HHS P01 CA089392NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS N01-HG-65403NHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01HG004438NHGRI NIH HHS U01 HG004446NIAAA NIH HHS R01 AA011330NIAAA NIH HHS R01 AA017535NIAAA NIH HHS R01 AA11330NIAAA NIH HHS U10 AA008401NIDA NIH HHS R01 DA012690NIDA NIH HHS R01 DA012849NIDA NIH HHS R01 DA013423NIDA NIH HHS R01 DA018432NIDA NIH HHS R01 DA12690NIDA NIH HHS R01 DA12849NIDA NIH HHS R01 DA18432NIDA NIH HHS RC2 DA028909
6 · The paper itself

Abstract

backgroundWe report a genome-wide association study (GWAS) of two populations, African-American and European-American (AA, EA) for opioid dependence (OD) in three sets of subjects, to identify pathways, genes, and alleles important in OD risk.

methodsThe design employed three phases (on the basis of separate sample collections). Phase 1 included our discovery GWAS dataset consisting of 5697 subjects (58% AA) diagnosed with opioid and/or other substance dependence and control subjects. Subjects were genotyped with the Illumina OmniQuad microarray, yielding 890,000 single nucleotide polymorphisms (SNPs) suitable for analysis. Additional genotypes were imputed with the 1000 Genomes reference panel. Top-ranked findings were further evaluated in Phase 2 by incorporating information from the publicly available Study of Addiction: Genetics and Environment dataset, with GWAS data from 4063 subjects (32% AA). In Phase 3, the most significant SNPs from Phase 2 were genotyped in 2549 independent subjects (32% AA). Analyses were performed with case-control and ordinal trait designs.

resultsMost significant results emerged from the AA subgroup. Genome-wide-significant associations (p < 5.0 × 10(-8)) were observed with SNPs from multiple loci-KCNG2*rs62103177 was most significant after combining results from datasets in every phase of the study. The most compelling results were obtained with genes involved in potassium signaling pathways (e.g., KCNC1 and KCNG2). Pathway analysis also implicated genes involved in calcium signaling and long-term potentiation.

conclusionsThis is the first study to identify risk variants for OD with GWAS. Our results strongly implicate risk pathways and provide insights into novel therapeutic and prevention strategies and might biologically bridge OD and other non-substance dependence psychiatric traits where similar pathways have been implicated.

Indexed as

Genome-Wide Association StudyAllelesBlack or African AmericanCalcium ChannelsCalcium SignalingDatabases, GeneticGenetic Predisposition to DiseaseGenotypeHumansLong-Term PotentiationOpioid-Related DisordersPolymorphism, Single NucleotidePotassiumPotassium Channels, Voltage-GatedSignal TransductionWhite PeopleCalcium ChannelsPotassiumPotassium Channels, Voltage-GatedCalcium signalingcomplex traitsconvergencegenome-wide associationopioid dependencepotassium

Identifiers

PMID24143882
PMCPMC3992201
OpenAlexW2098380904

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.