Evidence map›Paper›PMID 20713722›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Common genetic variation in Neuregulin 3 (NRG3) influences risk for schizophrenia and impacts NRG3 expression in human brain.

Wee-Tin Kao, Yanhong Wang, Joel E Kleinman, Barbara K Lipska, Thomas M Hyde, Daniel R Weinberger, Amanda J Law

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 2 pooled it
5.0field-weighted citation impact, top 4% 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

92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 128 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Effects of neuregulin 3 genotype on human prefrontal cortex physiology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014
    Trial
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Transcriptomic identification and developmental mapping ofTurkish journal of biology = Turk biyoloji dergisi · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. eLife · 2023
    Article
  16. Article
  17. Review
  18. Genetic Influences on Cognitive Dysfunction in Schizophrenia.Current topics in behavioral neurosciences · 2023
    Article
  19. Article
  20. Article

32 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

7 authors at 3 institutions in 1 country.

Wee-Tin KaoClinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1385, USA.
Yanhong Wang
Joel E Kleinman
Barbara K Lipska
Thomas M Hyde
Daniel R Weinberger
Amanda J Law
National Institutes of Health · USNational Institute of Mental Health · USHoward Hughes Medical Institute · US

Funding

Intramural NIH HHSMedical Research Council G120/997
6 · The paper itself

Abstract

Structural and polymorphic variations in Neuregulin 3 (NRG3), 10q22-23 are associated with a broad spectrum of neurodevelopmental disorders including developmental delay, cognitive impairment, autism, and schizophrenia. NRG3 is a member of the neuregulin family of EGF proteins and a ligand for the ErbB4 receptor tyrosine kinase that plays pleotropic roles in neurodevelopment. Several genes in the NRG-ErbB signaling pathway including NRG1 and ErbB4 have been implicated in genetic predisposition to schizophrenia. Previous fine mapping of the 10q22-23 locus in schizophrenia identified genome-wide significant association between delusion severity and polymorphisms in intron 1 of NRG3 (rs10883866, rs10748842, and rs6584400). The biological mechanisms remain unknown. We identified significant association of these SNPs with increased risk for schizophrenia in 350 families with an affected offspring and confirmed association to patient delusion and positive symptom severity. Molecular cloning and cDNA sequencing in human brain revealed that NRG3 undergoes complex splicing, giving rise to multiple structurally distinct isoforms. RNA expression profiling of these isoforms in the prefrontal cortex of 400 individuals revealed that NRG3 expression is developmentally regulated and pathologically increased in schizophrenia. Moreover, we show that rs10748842 lies within a DNA ultraconserved element and homedomain and strongly predicts brain expression of NRG3 isoforms that contain a unique developmentally regulated 5' exon (P = 1.097E(-12) to 1.445E(-15)). Our observations strengthen the evidence that NRG3 is a schizophrenia susceptibility gene, provide quantitative insight into NRG3 transcription traits in the human brain, and reveal a probable mechanistic basis for disease association.

Indexed as

Polymorphism, Single NucleotideAdolescentAdultAgedAged, 80 and overBlotting, WesternBrainCase-Control StudiesChildChild, PreschoolFamily HealthFemaleGene FrequencyGenetic Predisposition to DiseaseGenotypeHumansNeuregulinsNRG3 protein, human

Identifiers

PMID20713722
PMCPMC2932571
OpenAlexW2092143480

What OpenQuestion holds

Textmetadata
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.