Evidence map›Paper›PMID 26658939›Full record

ArticlePLoS genetics2015

Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

Neema Yazdani, Clarissa C Parker, Ying Shen, Eric R Reed, Michael A Guido, Loren A Kole, Stacey L Kirkpatrick, Jackie E Lim, Greta Sokoloff, Riyan Cheng and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

43 citing papers in PubMed, 63 citations in OpenAlex.

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  12. Differentially Expressed Genes inBiomolecules & therapeutics · 2022
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  19. Article
  20. Hnrnph1 is a novel regulator of alcohol reward.Drug and alcohol dependence · 2021
    Article
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

13 authors at 2 institutions in 1 country.

Neema YazdaniLaboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Clarissa C ParkerDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Ying ShenDivision of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Eric R ReedLaboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Michael A GuidoDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Loren A KoleDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Stacey L KirkpatrickLaboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Jackie E LimDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Greta SokoloffDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Riyan ChengDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
W Evan JohnsonDivision of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Abraham A PalmerDepartment of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America.
Camron D BryantLaboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States of America.
University of Chicago · USBoston University · US

Funding

Genetic Analysis of Developmental MutationsU01HD043430 · NICHD · BRIGHAM AND WOMEN'S HOSPITAL · PI BEIER, DAVID R. · 2002 to 2007
$5.5M
TRAINING IN BIOMOLECULAR PHARMACOLOGYT32GM008541 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARB, DAVID H · 1997 to 2022
$5.2M
Systems Genetic Analysis of Methamphetamine's Motivational Effects in a Mouse AILR01DA021336 · NIDA · UNIVERSITY OF CHICAGO · PI PALMER, ABRAHAM A · 2006 to 2015
$4.0M
Bridging genetic variation with behavior: Molecular and functional mechanisms of quantitative trait gene regulation of the stimulant and addictive properties of methamphetamine in miceR01DA039168 · NIDA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BRYANT, CAMRON D · 2015 to 2019
$3.0M
Statistical Tools and Methods for Next-Generation Sequencing in EpigeneticsR01HG005692 · NHGRI · BRIGHAM YOUNG UNIVERSITY · PI JOHNSON, WILLIAM EVAN · 2010 to 2014
$1.7M
Genetic Basis of Opioid Reward and Aversion in MiceR00DA029635 · NIDA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BRYANT, CAMRON D · 2013 to 2016
$750k
NHGRI NIH HHS R01 HG005692NHGRI NIH HHS R01HG005692NICHD NIH HHS U01 HD043430NIDA NIH HHS R00 DA029635NIDA NIH HHS R00DA029635NIDA NIH HHS R01 DA021336NIDA NIH HHS R01DA021336NIDA NIH HHS R01 DA039168NIDA NIH HHS R01DA039168NIGMS NIH HHS T32 GM008541NIGMS NIH HHS T32GM008541
6 · The paper itself

Abstract

Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL) mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp) that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J)-a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1) and RUN and FYVE domain-containing 1 (Rufy1). Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2), a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10-15). Transcription activator-like effector nucleases (TALENs)-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for prevention and treatment of substance abuse and possibly other psychiatric disorders.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsBehavior, AnimalCentral Nervous System StimulantsChromosome MappingDopaminergic NeuronsGenome-Wide Association StudyHeterogeneous-Nuclear RibonucleoproteinsHumansMaleMethamphetamineMiceMotor ActivityNuclear Receptor Subfamily 4, Group A, Member 2Quantitative Trait LociRNA, MessengerAdaptor Proteins, Signal TransducingCentral Nervous System StimulantsHeterogeneous-Nuclear RibonucleoproteinsMethamphetamineNr4a2 protein, mouseNuclear Receptor Subfamily 4, Group A, Member 2RNA, MessengerRufy1 protein, mouse

Identifiers

PMID26658939
PMCPMC4675533
OpenAlexW2192486264

What OpenQuestion holds

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LicenceCC BY
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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.