Evidence map›Paper›PMID 25403839›Full record

ArticleMolecular psychiatry2015

Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons.

T Yoshimizu, J Q Pan, A E Mungenast, J M Madison, S Su, J Ketterman, D Ongur, D McPhie, B Cohen, R Perlis and 1 more

Erratum issuedAbstract read
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In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Structure of a polymorphic repeat at theProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. The Impact of Overexpression of the Mouse Ortholog ofBiological psychiatry global open science · 2025
    Article
  7. Structure of a polymorphic repeat at themedRxiv : the preprint server for health sciences · 2025
    Article
  8. Reduced Gene Dosage of the Psychiatric Risk GeneInternational journal of molecular sciences · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023
    Review
  18. Article
  19. Article
  20. CACNA1C (CaNeuropharmacology · 2022
    Review

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

T Yoshimizu1] Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA [2] Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
J Q PanStanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
A E Mungenast1] Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA [2] Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
J M MadisonStanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
S Su1] Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA [2] Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
J KettermanStanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
D OngurMcLean Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
D McPhieMcLean Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
B CohenMcLean Hospital and Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
R Perlis1] Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA [2] Bipolar Clinic and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
L-H Tsai1] Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA [2] Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA [3] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.

Funding

The Cdk5/p35 KinaseR01NS051874 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2006 to 2015
$3.7M
The Epigenetics of Alzheimer's DiseaseR01NS078839 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2011 to 2015
$3.7M
Chemical Genomic Approaches to Neurobiology of DISC1R01MH091115 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2010 to 2014
$3.4M
Functional Studies of Variants of the Bipolar Risk Gene CACNA1C in Human NeuronsR21MH099448 · NIMH · BROAD INSTITUTE, INC. · PI PAN, JEN QIAN · 2012 to 2013
$467k
Epigenomic Characterization of Alzheimer's Disease Neurons from iPSCsRF1AG042978 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HAGGARTY, STEPHEN J, TSAI, LI-HUEI · 2012 to 2012
$429k
NIA NIH HHS RF1 AG042978NIA NIH HHS RF1-AG042978NIMH NIH HHS MH09395NIMH NIH HHS MH10028NIMH NIH HHS R01 MH091115NIMH NIH HHS R01-MH091115NIMH NIH HHS R21 MH099448NIMH NIH HHS R21MH099448-01NINDS NIH HHS R01 NS051874NINDS NIH HHS R01-NS051874NINDS NIH HHS R01 NS078839NINDS NIH HHS R01-NS078839
6 · The paper itself

Abstract

Psychiatric disorders have clear heritable risk. Several large-scale genome-wide association studies have revealed a strong association between susceptibility for psychiatric disorders, including bipolar disease, schizophrenia and major depression, and a haplotype located in an intronic region of the L-type voltage-gated calcium channel (VGCC) subunit gene CACNA1C (peak associated SNP rs1006737), making it one of the most replicable and consistent associations in psychiatric genetics. In the current study, we used induced human neurons to reveal a functional phenotype associated with this psychiatric risk variant. We generated induced human neurons, or iN cells, from more than 20 individuals harboring homozygous risk genotypes, heterozygous or homozygous non-risk genotypes at the rs1006737 locus. Using these iNs, we performed electrophysiology and quantitative PCR experiments that demonstrated increased L-type VGCC current density as well as increased mRNA expression of CACNA1C in iNs homozygous for the risk genotype, compared with non-risk genotypes. These studies demonstrate that the risk genotype at rs1006737 is associated with significant functional alterations in human iNs, and may direct future efforts at developing novel therapeutics for the treatment of psychiatric disease.

Indexed as

AdultAgedAstrocytesCalciumCalcium Channel AgonistsCalcium Channels, L-TypeCell DifferentiationCoculture TechniquesFemaleFibroblastsHumansIntercellular Signaling Peptides and ProteinsMaleMembrane PotentialsMental DisordersMiddle AgedCACNA1C protein, humanCACNA1D protein, humanCalciumCalcium Channel AgonistsCalcium Channels, L-TypeIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsTranscription Factors

Identifiers

PMID25403839
PMCPMC4394050

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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.