ArticleHuman molecular genetics2014
A population-based study of KCNH7 p.Arg394His and bipolar spectrum disorder.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Exome Sequencing of Familial Bipolar Disorder.JAMA psychiatry · 2016Pooled it
- Spinal muscular atrophy within Amish and Mennonite populations: Ancestral haplotypes and natural history.PloS one · 2018Trial
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- A rare variant inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Whole exome sequencing identifies KCNH7 variants associated with epilepsy in children.Genes & diseases · 2025Article
- Protective function of the voltage-gated potassium channel Kv11.3 in a mouse model of cardiac ischemia/reperfusion injury.PloS one · 2025Article
- Purkinje cell hyperexcitability and depressive-like behavior in mice lacking erg3 (ether-à-go-go-related gene) KScience advances · 2024Article
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- Genome-wide significant risk loci for mood disorders in the Old Order Amish founder population.Molecular psychiatry · 2023Article
- Adam, amigo, brain, and K channel.Biophysical reviews · 2023Review
- Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis.Journal of neural transmission (Vienna, Austria : 1996) · 2023Article
- Locus Coeruleus Neurons' Firing Pattern Is Regulated by ERG Voltage-Gated KInternational journal of molecular sciences · 2022Article
- Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types.Genome research · 2022Article
- A linkage and exome study of multiplex families with bipolar disorder implicates rare coding variants of ANK3 and additional rare alleles at 10q11-q21.Journal of psychiatry & neuroscience : JPN · 2021Article
- Kv11 (ether-à-go-go-related gene) voltage-dependent KThe Journal of physiology · 2021Article
- Whole-exome sequencing of 81 individuals from 27 multiply affected bipolar disorder families.Translational psychiatry · 2020Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 1 country.
Funding
Abstract
We conducted blinded psychiatric assessments of 26 Amish subjects (52 ± 11 years) from four families with prevalent bipolar spectrum disorder, identified 10 potentially pathogenic alleles by exome sequencing, tested association of these alleles with clinical diagnoses in the larger Amish Study of Major Affective Disorder (ASMAD) cohort, and studied mutant potassium channels in neurons. Fourteen of 26 Amish had bipolar spectrum disorder. The only candidate allele shared among them was rs78247304, a non-synonymous variant of KCNH7 (c.1181G>A, p.Arg394His). KCNH7 c.1181G>A and nine other potentially pathogenic variants were subsequently tested within the ASMAD cohort, which consisted of 340 subjects grouped into controls subjects and affected subjects from overlapping clinical categories (bipolar 1 disorder, bipolar spectrum disorder and any major affective disorder). KCNH7 c.1181G>A had the highest enrichment among individuals with bipolar spectrum disorder (χ(2) = 7.3) and the strongest family-based association with bipolar 1 (P = 0.021), bipolar spectrum (P = 0.031) and any major affective disorder (P = 0.016). In vitro, the p.Arg394His substitution allowed normal expression, trafficking, assembly and localization of HERG3/Kv11.3 channels, but altered the steady-state voltage dependence and kinetics of activation in neuronal cells. Although our genome-wide statistical results do not alone prove association, cumulative evidence from multiple independent sources (parallel genome-wide study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data) implicates neuronal HERG3/Kv11.3 potassium channels in the pathophysiology of bipolar spectrum disorder. Such a finding, if corroborated by future studies, has implications for mental health services among the Amish, as well as development of drugs that specifically target HERG3/Kv11.3.
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Registered trials
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