ArticleFrontiers in genetics2013
Converging Evidence for Epistasis between ANK3 and Potassium Channel Gene KCNQ2 in Bipolar Disorder.
Article in Frontiers in genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Bipolar Disorder in a female with CDKL5 Deficiency Disorder: A Case Report.Research square · 2024Article
- Exploring the genetic correlation of cardiovascular diseases and mood disorders in the UK Biobank.Epidemiology and psychiatric sciences · 2023Article
- Genetic and environment effects on structural neuroimaging endophenotype for bipolar disorder: a novel molecular approach.Translational psychiatry · 2022Article
- Genetic contributions to bipolar disorder: current status and future directions.Psychological medicine · 2021Review
- Translational genomics and beyond in bipolar disorder.Molecular psychiatry · 2021Review
- Neurological Disorders and Risk of Arrhythmia.International journal of molecular sciences · 2020Review
- The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases.Biomedicines · 2020Review
- Differential Dorsolateral Prefrontal Cortex Proteomic Profiles of Suicide Victims with Mood Disorders.Genes · 2020Article
- Pharmacological Manipulation of KFrontiers in physiology · 2020Review
- Lithium improved behavioral and epileptic symptoms in an adolescent with ring chromosome 20 and bipolar disorder not otherwise specified.Clinical case reports · 2018Article
- A Schizophrenia-Related Deletion Leads to KCNQ2-Dependent Abnormal Dopaminergic Modulation of Prefrontal Cortical Interneuron Activity.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.Genes, brain, and behavior · 2017Article
- Autism spectrum disorder and epileptic encephalopathy: common causes, many questions.Journal of neurodevelopmental disorders · 2017Review
- Dissecting bipolar disorder complexity through epigenomic approach.Molecular psychiatry · 2016Review
- Genetic and childhood trauma interaction effect on age of onset in bipolar disorder: An exploratory analysis.Journal of affective disorders · 2015Article
- Review
- Genetic underpinnings of white matter 'connectivity': heritability, risk, and heterogeneity in schizophrenia.Schizophrenia research · 2015Review
- Editorial: "Ion channels and mental illness: exploring etiology and pathophysiology in major psychiatric disorders".Frontiers in genetics · 2015Article
- Analysis of ANK3 and CACNA1C variants identified in bipolar disorder whole genome sequence data.Bipolar disorders · 2014Article
- The node of Ranvier in CNS pathology.Acta neuropathologica · 2014Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Genome-wide association studies (GWAS) have implicated ANK3 as a susceptibility gene for bipolar disorder (BP). We examined whether epistasis with ANK3 may contribute to the "missing heritability" in BP. We first identified via the STRING database 14 genes encoding proteins with prior biological evidence that they interact molecularly with ANK3. We then tested for statistical evidence of interactions between SNPs in these genes in association with BP in a discovery GWAS dataset and two replication GWAS datasets. The most significant interaction in the discovery GWAS was between SNPs in ANK3 and KCNQ2 (p = 3.18 × 10(-8)). A total of 31 pair-wise interactions involving combinations between two SNPs from KCNQ2 and 16 different SNPs in ANK3 were significant after permutation. Of these, 28 pair-wise interactions were significant in the first replication GWAS. None were significant in the second replication GWAS, but the two SNPs from KCNQ2 were found to significantly interact with five other SNPs in ANK3, suggesting possible allelic heterogeneity. KCNQ2 forms homo- and hetero-meric complexes with KCNQ3 that constitute voltage-gated potassium channels in neurons. ANK3 is an adaptor protein that, through its interaction with KCNQ2 and KCNQ3, directs the localization of this channel in the axon initial segment (AIS). At the AIS, the KCNQ2/3 complex gives rise to the M-current, which stabilizes the neuronal resting potential and inhibits repetitive firing of action potentials. Thus, these channels act as "dampening" components and prevent neuronal hyperactivity. The interactions between ANK3 and KCNQ2 merit further investigation, and if confirmed, may motivate a new line of research into a novel therapeutic target for BP.
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