ArticleMolecular psychiatry2016
Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.Molecular psychiatry · 2021Pooled it
- Meta-analysis of genomic variants and gene expression data in schizophrenia suggests the potential need for adjunctive therapeutic interventions for neuropsychiatric disorders.Journal of genetics · 2019Pooled it
- A Genetic Landscape of Euploid Miscarriages From Couples With Recurrent Pregnancy Loss Through Whole Exome Sequencing.Molecular genetics & genomic medicine · 2026Article
- Single-molecule DNA analysis implicates brain mitochondria pathology in bipolar disorder.Molecular psychiatry · 2025Article
- Mosaic variants of neurodevelopmental and mitochondrial genes in postmortem paraventricular thalamus in bipolar disorder detected by deep exome sequencing.Psychiatry and clinical neurosciences · 2025Article
- Biallelic TEDC1 variants cause a new syndrome with severe growth impairment and endocrine complications.European journal of human genetics : EJHG · 2025Article
- Copy number variations in RNF216 and postsynaptic membrane-associated genes are associated with bipolar disorder: a case-control study in the Japanese population.Psychiatry and clinical neurosciences · 2025Article
- A Brief Introduction to Genomics and Single-cell Analysis for Psychiatric Disorders.Juntendo medical journal · 2025Review
- Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide.Frontiers in cell and developmental biology · 2024Review
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Deep exome sequencing identifies enrichment of deleterious mosaic variants in neurodevelopmental disorder genes and mitochondrial tRNA regions in bipolar disorder.Molecular psychiatry · 2023Article
- Role of microtubule actin crosslinking factor 1 (MACF1) in bipolar disorder pathophysiology and potential in lithium therapeutic mechanism.Translational psychiatry · 2023Review
- Neurite outgrowth deficits caused by rare PLXNB1 mutation in pediatric bipolar disorder.Molecular psychiatry · 2023Article
- Cryptic mutations of PLC family members in brain disorders: recent discoveries and a deep-learning-based approach.Brain : a journal of neurology · 2023Review
- Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects.Genome biology · 2023Article
- Prevalence and Penetrance of Rare Pathogenic Variants in Neurodevelopmental Psychiatric Genes in a Health Care System Population.The American journal of psychiatry · 2023Article
- Molecular Mechanisms Underlying CaInternational journal of molecular sciences · 2022Review
- Mutations in trpγ, the homologue of TRPC6 autism candidate gene, causes autism-like behavioral deficits in Drosophila.Molecular psychiatry · 2022Article
- dbBIP: a comprehensive bipolar disorder database for genetic research.Database : the journal of biological databases and curation · 2022Article
- Two Genetic Mechanisms in Two Siblings with Intellectual Disability, Autism Spectrum Disorder, and Psychosis.Journal of personalized medicine · 2022Article
7 more citing papers are in PubMed but not listed here.
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9 authors.
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Abstract
Although numerous genetic studies have been conducted for bipolar disorder (BD), its genetic architecture remains elusive. Here we perform, to the best of our knowledge, the first trio-based exome sequencing study for BD to investigate potential roles of de novo mutations in the disease etiology. We identified 71 de novo point mutations and one de novo copy-number mutation in 79 BD probands. Among the genes hit by de novo loss-of-function (LOF; nonsense, splice site or frameshift) or protein-altering (LOF, missense and inframe indel) mutations, we found significant enrichment of genes highly intolerant (first percentile of intolerant genes assessed by Residual Variation Intolerance Score) to protein-altering variants in general population, an observation that is also reported in autism and schizophrenia. When we performed a joint analysis using the data of schizoaffective disorder in published studies, we found global enrichment of de novo LOF and protein-altering mutations in the combined group of bipolar I and schizoaffective disorders. Considering relationship between de novo mutations and clinical phenotypes, we observed significantly earlier disease onset among the BD probands with de novo protein-altering mutations when compared with non-carriers. Gene ontology enrichment analysis of genes hit by de novo protein-altering mutations in bipolar I and schizoaffective disorders did not identify any significant enrichment. These results of exploratory analyses collectively point to the roles of de novo LOF and protein-altering mutations in the etiology of bipolar disorder and warrant further large-scale studies.
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