Evidence map›Paper›PMID 24348429›Full record

ArticleFrontiers in psychiatry2013

Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways.

Berit Kerner, Aliz R Rao, Bryce Christensen, Sugandha Dandekar, Michael Yourshaw, Stanley F Nelson

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 3 pooled it
3.9field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 3 syntheses or guidelines pooled it, 43 citations in OpenAlex.

  1. Pooled it
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  12. The Golgin Protein Giantin Regulates Interconnections Between Golgi Stacks.Frontiers in cell and developmental biology · 2019
    Article
  13. Article
  14. From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Review
  15. [Genetics of bipolar disorder].Der Nervenarzt · 2017
    Review
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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

6 authors at 2 institutions in 1 country.

Berit KernerSemel Institute for Neuroscience and Human Behavior, University of California Los Angeles , Los Angeles, CA , USA.
Aliz R RaoDepartment of Human Genetics, University of California Los Angeles , Los Angeles, CA , USA.
Bryce ChristensenGolden Helix , Bozeman, MT , USA.
Sugandha DandekarDepartment of Human Genetics, University of California Los Angeles , Los Angeles, CA , USA.
Michael YourshawDepartment of Human Genetics, University of California Los Angeles , Los Angeles, CA , USA.
Stanley F NelsonDepartment of Human Genetics, University of California Los Angeles , Los Angeles, CA , USA ; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles , Los Angeles, CA , USA ; Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA , USA.
University of California, Los Angeles · USDouble Helix (United States) · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
Symptom Dimensions in PsychosisK08MH074057 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KERNER, BERIT · 2005 to 2009
$872k
Parsing of Bipolar Disorders and Schizophrenia: A Latent Class ApproachR01MH085744 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KERNER, BERIT · 2010 to 2012
$723k
NCATS NIH HHS UL1 TR000124NHGRI NIH HHS T32 HG002536NIMH NIH HHS K08 MH074057NIMH NIH HHS R01 MH085744Wellcome Trust
6 · The paper itself

Abstract

Bipolar disorder is a common, complex, and severe psychiatric disorder with cyclical disturbances of mood and a high suicide rate. Here, we describe a family with four siblings, three affected females and one unaffected male. The disease course was characterized by early-onset bipolar disorder and co-morbid anxiety spectrum disorders that followed the onset of bipolar disorder. Genetic risk factors were suggested by the early onset of the disease, the severe disease course, including multiple suicide attempts, and lack of adverse prenatal or early life events. In particular, drug and alcohol abuse did not contribute to the disease onset. Exome sequencing identified very rare, heterozygous, and likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C, GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among all three affected family members but absent in the unaffected sibling and in more than 200 controls. The genes encode proteins with significant regulatory roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These pathways are central to neuronal and synaptic plasticity, cognition, affect regulation and response to chronic stress. In addition, proteins in these pathways are the target of commonly used mood-stabilizing drugs, such as tricyclic antidepressants, lithium, and valproic acid. The combination of multiple rare, damaging mutations in these central pathways could lead to reduced resilience and increased vulnerability to stressful life events. Our results support a new model for psychiatric disorders, in which multiple rare, damaging mutations in genes functionally related to a common signaling pathway contribute to the manifestation of bipolar disorder.

Indexed as

bipolar disorderERK/MAPK and CREB-regulated intracellular signaling pathwayexome sequencinggenetic risk factorsneuronal plasticityrare-variant common-disease modelstress responsethreshold disease model

Identifiers

PMID24348429
PMCPMC3842585
OpenAlexW2142136918

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.