Evidence map›Paper›PMID 36171425›Full record

SynthesisNature neuroscience2022

Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.

Rachel L Kember, Rachel Vickers-Smith, Heng Xu, Sylvanus Toikumo, Maria Niarchou, Hang Zhou, Emily E Hartwell, Richard C Crist, Christopher T Rentsch, Million Veteran Program and 6 more

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 5 pooled it
12.8field-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

82 citing papers in PubMed, 5 syntheses or guidelines pooled it, 96 citations in OpenAlex.

  1. Pooled it
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  3. Multi-ancestry genome-wide association meta-analysis of buprenorphine treatment response.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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  9. 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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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

16 authors at 7 institutions in 2 countries.

Rachel L KemberMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8820-2659
Rachel Vickers-SmithMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
Heng XuDepartment of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Sylvanus ToikumoDepartment of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Maria NiarchouDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-8855-7393
Hang ZhouVeterans Affairs Connecticut Healthcare System, West Haven, CT, USA.ORCID http://orcid.org/0000-0002-7694-6391
Emily E HartwellMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5137-9714
Richard C CristMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
Christopher T RentschVeterans Affairs Connecticut Healthcare System, West Haven, CT, USA.ORCID http://orcid.org/0000-0002-1408-7907
Million Veteran Program
Lea K DavisDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Amy C JusticeVeterans Affairs Connecticut Healthcare System, West Haven, CT, USA.ORCID http://orcid.org/0000-0003-0139-5502
Sandra Sanchez-RoigeDepartment of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-6137-5699
Kyle M KampmanMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA.
Joel GelernterVeterans Affairs Connecticut Healthcare System, West Haven, CT, USA.ORCID http://orcid.org/0000-0002-4067-1859
Henry R KranzlerMental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA. kranzler@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-1018-0450
University of Pennsylvania · USYale University · USVA Connecticut Healthcare System · USVanderbilt University Medical Center · USPhiladelphia VA Medical Center · USUniversity of California San Diego · USUniversity of Kentucky · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Radiochemistry CoreP30DA046345 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI KRANZLER, HENRY RICHARD, MACH, ROBERT H · 2019 to 2023
$9.4M
Characterizing the phenotypic spectrum associated with genetic liability for alcohol use disorderK01AA028292 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI KEMBER, RACHEL LORRAINE · 2021 to 2024
$505k
BLRD VA I01 BX003341CSRD VA I01 CX001734NCATS NIH HHS UL1 TR001863NIAAA NIH HHS K01 AA028292NIDA NIH HHS P30 DA046345
6 · The paper itself

Abstract

Despite an estimated heritability of ~50%, genome-wide association studies of opioid use disorder (OUD) have revealed few genome-wide significant loci. We conducted a cross-ancestry meta-analysis of OUD in the Million Veteran Program (N = 425,944). In addition to known exonic variants in OPRM1 and FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1 and KCNN1. A meta-analysis including other datasets identified a locus in TSNARE1. In total, we identified 14 loci for OUD, 12 of which are novel. Significant genetic correlations were identified for 127 traits, including psychiatric disorders and other substance use-related traits. The only significantly enriched cell-type group was CNS, with gene expression enrichment in brain regions previously associated with substance use disorders. These findings increase our understanding of the biological basis of OUD and provide further evidence that it is a brain disease, which may help to reduce stigma and inform efforts to address the opioid epidemic.

Indexed as

Behavior, AddictiveOpioid-Related DisordersBrainFurinGenome-Wide Association StudyHumansFurin

Identifiers

PMID36171425
PMCPMC9682545
OpenAlexW4297498066

What OpenQuestion holds

Textmetadata
LicenceTDM
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.