Evidence map›Paper›PMID 25744370›Full record

SynthesisBiological psychiatry2015

Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.

Dana B Hancock, Joshua L Levy, Nathan C Gaddis, Cristie Glasheen, Nancy L Saccone, Grier P Page, Gary K Hulse, Dieter Wildenauer, Erin A Kelty, Sibylle G Schwab and 11 more

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

Synthesis in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 3 pooled it
9.6field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 9 institutions in 3 countries.

Dana B HancockBehavioral Health Epidemiology Program, Behavioral Health and Criminal Justice Division, Research Triangle Institute (RTI) International, St. Louis, Missouri.. Electronic address: dhancock@rti.org.
Joshua L LevyResearch Computing Division, RTI International, Research Triangle Park, North Carolina, St. Louis, Missouri.
Nathan C GaddisResearch Computing Division, RTI International, Research Triangle Park, North Carolina, St. Louis, Missouri.
Cristie GlasheenBehavioral Health Epidemiology Program, Behavioral Health and Criminal Justice Division, Research Triangle Institute (RTI) International, St. Louis, Missouri.
Nancy L SacconeDepartment of Genetics, Washington University in St. Louis, St. Louis, Missouri.
Grier P PageCenter for Public Health Genomics, RTI International, Atlanta, Georgia.
Gary K HulseSchool of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
Dieter WildenauerSchool of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
Erin A KeltySchool of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
Sibylle G SchwabDepartment of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.; Faculty of Science, Medicine, and Health, University of Wollongong, Wollongong, New South Wales.
Louisa DegenhardtNational Drug and Alcohol Research Centre, University of New South Wales, Sydney.
Nicholas G MartinQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland.
Grant W MontgomeryQueensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland.
John AttiaCentre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales.; Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales.
Elizabeth G HollidayCentre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales.; Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales.
Mark McEvoyCentre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales.; Public Health Research Program, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales.
Rodney J ScottCenter for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales.; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales.; Division of Genetics, Hunter Area Pathology Service, Newcastle, New South Wales, Australia.
Laura J BierutDepartment of Psychiatry, Washington University in St. Louis, St. Louis, Missouri.
Elliot C NelsonDepartment of Psychiatry, Washington University in St. Louis, St. Louis, Missouri.
Alex H KralUrban Health Program, Behavioral Health and Criminal Justice Division, RTI International, San Francisco, California.
Eric O JohnsonFellow Program and Behavioral Health and Criminal Justice Division, RTI International, Research Triangle Park, North Carolina.
RTI International · USHunter Medical Research Institute · AUThe University of Western Australia · AUWashington University in St. Louis · USQIMR Berghofer Medical Research Institute · AUFriedrich-Alexander-Universität Erlangen-Nürnberg · DEOffice of Public Health Genomics · USSan Francisco Department of Public Health · USUNSW Sydney · AU

Funding

Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI JAY Arnold TISCHFIELD · 1989 to 2026
$162.7M
Targeting the p53 pathway for reversal of oral premalignancyP50CA097007 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LEE, HO-YOUNG · 2002 to 2012
$26.1M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
UT M.D. Anderson Cancer Center SPORE in MelanomaP50CA093459 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GRIMM, ELIZABETH A · 2004 to 2014
$23.7M
GENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2M
Multiethnic Cohort Study of Diet and CancerR37CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 2003 to 2012
$23.2M
VALIDATION OF A DIET HISTORY METHOD FOR EPIDEMIOLOGIC STUDIES OF CANCERP01CA033619 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 1985 to 2010
$18.5M
Enhancing the Effectiveness of Varenicline Based Smoking Cessation TreatmentR01HL109031 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI BAKER, TIMOTHY B, STEIN, JAMES H · 2011 to 2020
$17.5M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2005 to 2019
$17.3M
The Collaborative Genetic Study of Nicotine DependenceP01CA089392 · NCI · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2001 to 2012
$17.3M
Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3U01CA098758 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2003 to 2010
$11.0M
A Genome-wide Association Study of Prostate Cancer in African AmericansU01CA136792 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2009 to 2011
$9.4M
NCI NIH HHS P01 CA033619NCI NIH HHS P01 CA089392NCI NIH HHS P01 CA33619NCI NIH HHS P50 CA084724NCI NIH HHS P50 CA093459NCI NIH HHS P50CA093459NCI NIH HHS P50 CA097007NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA133996NCI NIH HHS R01 CA63464NCI NIH HHS R37 CA054281NCI NIH HHS R37 CA54281NCI NIH HHS RC2 CA148085NCI NIH HHS U01 CA098758NCI NIH HHS U01 CA136792NCI NIH HHS U01 CA98758NCRR NIH HHS M01 RR165001NCRR NIH HHS M01RR165001NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS N01 HG065403NHGRI NIH HHS U01 HG004422NHGRI NIH HHS U01 HG004436NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01HG004438NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01 HG004726NHGRI NIH HHS U01 HG004789NHGRI NIH HHS X01 HG005274NHGRI NIH HHS X01HG005274NHLBI NIH HHS HHSN268200782096CNHLBI NIH HHS R01 HL109031NIAAA NIH HHS R01 AA011330NIAAA NIH HHS U10 AA008401NIDA NIH HHS P50 DA019706NIDA NIH HHS R01 DA013423NIDA NIH HHS R01 DA017305NIDA NIH HHS R01 DA019963NIDA NIH HHS R01 DA025888NIDA NIH HHS R01 DA026141NIDA NIH HHS R01 DA026911NIDA NIH HHS R01 DA036583NIDA NIH HHS R01DA036583NIDA NIH HHS R01 DA17305NIDA NIH HHS R33 DA027486NIDA NIH HHS R33DA027486NIDDK NIH HHS P30 DK072488NIEHS NIH HHS R01 ES011740NINDS NIH HHS R01 NS045012NINDS NIH HHS R01 NS45012NINDS NIH HHS R01NS45012PHS HHS U01G004446
6 · The paper itself

Abstract

backgroundNo opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility. We used evidence of polymorphisms altering OPRM1 expression in normal human brain tissue to nominate and then test associations with heroin addiction.

methodsWe tested 103 OPRM1 SNPs for association with OPRM1 messenger RNA expression in prefrontal cortex from 224 European Americans and African Americans of the BrainCloud cohort. We then tested the 16 putative cis-expression quantitative trait loci (cis-eQTL) SNPs for association with heroin addiction in the Urban Health Study and two replication cohorts, totaling 16,729 European Americans, African Americans, and Australians of European ancestry.

resultsFour putative cis-eQTL SNPs were significantly associated with heroin addiction in the Urban Health Study (smallest p = 8.9 × 10(-5)): rs9478495, rs3778150, rs9384169, and rs562859. Rs3778150, located in OPRM1 intron 1, was significantly replicated (p = 6.3 × 10(-5)). Meta-analysis across all case-control cohorts resulted in p = 4.3 × 10(-8): the rs3778150-C allele (frequency = 16%-19%) being associated with increased heroin addiction risk. Importantly, the functional SNP allele rs1799971-A was associated with heroin addiction only in the presence of rs3778150-C (p = 1.48 × 10(-6) for rs1799971-A/rs3778150-C and p = .79 for rs1799971-A/rs3778150-T haplotypes). Lastly, replication was observed for six other intron 1 SNPs that had prior suggestive associations with heroin addiction (smallest p = 2.7 × 10(-8) for rs3823010).

conclusionsOur findings show that common OPRM1 intron 1 SNPs have replicable associations with heroin addiction. The haplotype structure of rs3778150 and nearby SNPs may underlie the inconsistent associations between rs1799971 and heroin addiction.

Indexed as

Polymorphism, Single NucleotideAdolescentAdultAgedAustraliaBlack or African AmericanCase-Control StudiesChildChild, PreschoolCohort StudiesFemaleHeroin DependenceHumansInfantInfant, NewbornMaleOPRM1 protein, humanReceptors, Opioid, muRNA, MessengerGenetic association studyHeroinMultiancestryOpioidOPRM1Prefrontal cortex

Identifiers

PMID25744370
PMCPMC4519434
OpenAlexW2085277613

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Registered trials

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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.