ArticleMolecular psychiatry2020
Integrative analyses prioritize GNL3 as a risk gene for bipolar disorder.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A beginner's guide on the use of brain organoids for neuroscientists: a systematic review.Stem cell research & therapy · 2023Pooled it
- Parallel Single-Tissue Summary-Data Mendelian Randomization and Functional Validation Identify the ARRDC1 Promoter SNP rs4494021 as a Genetic Marker Associated with Anxiety Disorders.Neuropsychiatric disease and treatment · 2026Article
- Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.International journal of molecular sciences · 2025Review
- Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025Review
- Protein Arginine Methyltransferases from Regulatory Function to Clinical Implication in Central Nervous System.Cellular and molecular neurobiology · 2025Review
- Genomic SEM applied to explore etiological divergences in bipolar subtypes.Psychological medicine · 2024Article
- Emerging roles of RNA binding proteins in intervertebral disc degeneration and osteoarthritis.Orthopaedic surgery · 2023Review
- Integrative analyses highlight functional regulatory variants associated with neuropsychiatric diseases.Nature genetics · 2023Article
- Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways.Nature communications · 2023Article
- Human forebrain organoids-based multi-omics analyses reveal PCCB's regulation on GABAergic system contributing to schizophrenia.Research square · 2023Article
- Cellular Genome-wide Association Study Identifies Common Genetic Variation Influencing Lithium-Induced Neural Progenitor Proliferation.Biological psychiatry · 2023Article
- Genomic regulatory sequences in the pathogenesis of bipolar disorder.Frontiers in psychiatry · 2023Review
- A Local Genetic Correlation Analysis Provides Biological Insights Into the Shared Genetic Architecture of Psychiatric and Substance Use Phenotypes.Biological psychiatry · 2022Article
- Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings.Molecular psychiatry · 2022Review
- Powerful and robust inference of complex phenotypes' causal genes with dependent expression quantitative loci by a median-based Mendelian randomization.American journal of human genetics · 2022Article
- Association of Nucleostemin Polymorphisms with Chronic Hepatitis B Virus Infection in Chinese Han Population.Genetic testing and molecular biomarkers · 2022Article
- Human forebrain organoids reveal connections between valproic acid exposure and autism risk.Translational psychiatry · 2022Article
- GNL3 Regulates SIRT1 Transcription and Promotes Hepatocellular Carcinoma Stem Cell-Like Features and Metastasis.Journal of oncology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) associated with bipolar disorder (BD), but what the causal variants are and how they contribute to BD is largely unknown. In this study, we used FUMA, a GWAS annotation tool, to pinpoint potential causal variants and genes from the latest BD GWAS findings, and performed integrative analyses, including brain expression quantitative trait loci (eQTL), gene coexpression network, differential gene expression, protein-protein interaction, and brain intermediate phenotype association analysis to identify the functions of a prioritized gene and its connection to BD. Convergent lines of evidence prioritized protein-coding gene G Protein Nucleolar 3 (GNL3) as a BD risk gene, with integrative analyses revealing GNL3's roles in cell proliferation, neuronal functions, and brain phenotypes. We experimentally revealed that BD-related eQTL SNPs rs10865973, rs12635140, and rs4687644 regulate GNL3 expression using dual luciferase reporter assay and CRISPR interference experiment in human neural progenitor cells. We further identified that GNL3 knockdown and overexpression led to aberrant neuronal proliferation and differentiation, using two-dimensional human neural cell cultures and three-dimensional forebrain organoid model. This study gathers evidence that BD-related genetic variants regulate GNL3 expression which subsequently affects neuronal proliferation and differentiation.
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