ArticleBiological psychiatry2023
Cellular Genome-wide Association Study Identifies Common Genetic Variation Influencing Lithium-Induced Neural Progenitor Proliferation.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Dynamic neuro-immune regulation of psychiatric risk loci in human neurons.Nature communications · 2026Article
- Assessing molecular gene by treatment interactions using a population of neural progenitors exposed to valproic acid and lithium.Molecular psychiatry · 2026Article
- Enolase 2-mediated lactylation-dependent disruption of the GNL3-MDM2-p53 axis in age-related osteoarthritis.Cellular & molecular biology letters · 2026Article
- Perfluorooctanoic acid (PFOA) induces lipid accumulation, oxidative stress, and reduced neurogenesis in primary human neuronal progenitor cells.Frontiers in toxicology · 2026Article
- Cell villages and Dirichlet modeling map human cell fitness genetics.bioRxiv : the preprint server for biology · 2025Article
- Probabilistic classification of gene-by-treatment interactions on molecular count phenotypes.PLoS genetics · 2025Article
- Stimulating Wnt signaling reveals context-dependent genetic effects on gene regulation in primary human neural progenitors.Nature neuroscience · 2024Article
- Schizophrenia genomics: genetic complexity and functional insights.Nature reviews. Neuroscience · 2024Review
- Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models.Translational psychiatry · 2024Article
- Pharmacogenomics and response to lithium in bipolar disorder.Pharmacogenomics · 2024Review
- Low-dose lithium adjunct to atypical antipsychotic treatment nearly improved cognitive impairment, deteriorated the gray-matter volume, and decreased the interleukin-6 level in drug-naive patients with first schizophrenia symptoms: a follow-up pilot study.Schizophrenia (Heidelberg, Germany) · 2023Article
- Single-cell genomics meets human genetics.Nature reviews. Genetics · 2023Review
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11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBipolar disorder is a highly heritable neuropsychiatric condition affecting more than 1% of the human population. Lithium salts are commonly prescribed as a mood stabilizer for individuals with bipolar disorder. Lithium is clinically effective in approximately half of treated individuals, and their genetic backgrounds are known to influence treatment outcomes. While the mechanism of lithium's therapeutic action is unclear, it stimulates adult neural progenitor cell proliferation, similar to some antidepressant drugs.
methodsTo identify common genetic variants that modulate lithium-induced proliferation, we conducted an EdU incorporation assay in a library of 80 genotyped human neural progenitor cells treated with lithium. These data were used to perform a genome-wide association study to identify common genetic variants that influence lithium-induced neural progenitor cell proliferation. We manipulated the expression of a putatively causal gene using CRISPRi/a (clustered regularly interspaced short palindromic repeats interference/activation) constructs to experimentally verify lithium-induced proliferation effects.
resultsWe identified a locus on chr3p21.1 associated with lithium-induced proliferation. This locus is also associated with bipolar disorder risk, schizophrenia risk, and interindividual differences in intelligence. We identified a single gene, GNL3, whose expression temporally increased in an allele-specific fashion following lithium treatment. Experimentally increasing the expression of GNL3 led to increased proliferation under baseline conditions, while experimentally decreasing GNL3 expression suppressed lithium-induced proliferation.
conclusionsOur experiments reveal that common genetic variation modulates lithium-induced neural progenitor proliferation and that GNL3 expression is necessary for the full proliferation-stimulating effects of lithium. These results suggest that performing genome-wide associations in genetically diverse human cell lines is a useful approach to discover context-specific pharmacogenomic effects.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.