The genetics of bipolar disorder

Barnett, J.H.; Smoller, J.W.

doi:10.1016/j.neuroscience.2009.03.080

Cited by 407Bipolar Disorder and TreatmentGenetic Associations and EpidemiologySchizophrenia research and treatment

The genetics of bipolar disorder

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Barnett, J.H., Smoller, J.W.·2009·Neuroscience

DOI 10.1016/j.neuroscience.2009.03.080PMC PMC3637882

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Abstract

Bipolar disorder is a mood disorder characterized by impairing episodes of mania and depression. Twin studies have established that bipolar disorder is among the most heritable of medical disorders and efforts to identify specific susceptibility genes have intensified over the past two decades. The search for genes influencing bipolar disorder has been complicated by a paucity of animal models, limited understanding of pathogenesis, and the genetic and phenotypic complexity of the syndrome. Linkage studies have implicated several chromosomal regions as harboring relevant genes, but results have been inconsistent. It is now widely accepted that the genetic liability to bipolar disorder reflects the action of many genes of individually small effect, a scenario for which linkage studies are poorly suited. Thus, association studies, which are more powerful for the detection of modest effect loci, have become the focus of gene-finding research. A large number of candidate genes, including biological candidates derived from hypotheses about the pathogenesis of the disorder and positional candidates derived from linkage and cytogenetic studies, have been evaluated. Several of these genes have been associated with the disorder in independent studies (including BDNF, DAOA, DISC1, GRIK4, SLC6A4, and TPH2), but none has been established. The clinical heterogeneity of bipolar disorder and its phenotypic and genetic overlap with other disorders (especially schizophrenia, schizoaffective disorder, and major depressive disorder) have raised questions about the optimal phenotype definition for genetic studies. Nevertheless, genomewide association analysis, which has successfully identified susceptibility genes for a variety of complex disorders, has begun to implicate specific genes for bipolar disorder (DGKH, CACNA1C, ANK3). The polygenicity of the disorder means that very large samples will be needed to detect the modest effect loci that likely contribute to bipolar disorder. Detailed genetic dissection of the disorder may provide novel targets (both pharmacologic and psychosocial) for intervention.

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Monozygotic twins and first-degree relatives also have an increased likelihood of developing psychotic, bipolar or common mental disorders.
“Monozygotic twins 123-126 and first-degree relatives (depending on the number of probands) 127-130 also have an increased likelihood of developing these disorders.”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [124]
Monozygotic twins have a concordance rate of 45% for bipolar disorder.
“Twins (monozygotic concordance rate 45%) 124 *”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [124]

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Authors: Barnett, J. H., & Smoller, J. W.
Affiliations: University of Cambridge (GB)
Massachusetts General Hospital (US)
Corresponding author: Smoller, J.W.
ORCID: Barnett, J.H.
Smoller, J.W.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2009-11
Volume: 164
Issue: 1
Pages: 331-343
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2009.03.080
PMC: PMC3637882
OpenAlex: W2008741245
Cited by: 407
References: 147
Citations by year: 2026: 13 · 2025: 21 · 2024: 21 · 2023: 19 · 2022: 19 · 2021: 40 · 2020: 26 · 2019: 41 · 2018: 19 · 2017: 20 · 2016: 28 · 2015: 18 · 2014: 25 · 2013: 21 · 2012: 26
FWCI: 3.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R01MH079799)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords: bipolar disorder, genetic susceptibility, heritability, candidate genes, genome-wide association study, polygenic liability, CACNA1C, ANK3, brain-derived neurotrophic factor, DAOA, DISC1, GRIK4, serotonin transporter, tryptophan hydroxylase 2, schizophrenia, schizoaffective disorder, major depressive disorder, phenotype definition, genetic heterogeneity
MeSH terms: Animals, Bipolar Disorder, Humans, Genetic Predisposition to Disease

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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The genetics of bipolar disorder

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