ArticleBiological psychiatry2024
A Single-Nucleus Transcriptome-Wide Association Study Implicates Novel Genes in Depression Pathogenesis.
Article in Biological psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Recent developments in omics studies and artificial intelligence in depression and suicide.Translational psychiatry · 2025Pooled it
- GROMTools: scalable individual-level GReX imputation for mega-biobank-scale cohorts.Bioinformatics (Oxford, England) · 2026Article
- Article
- Cellular transcriptomic signatures underpinning the heterogeneity of depression in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A diagnostic plasma omics-biomarker for Alzheimer's disease informed by microglial single-cell transcriptomics: A pilot study.bioRxiv : the preprint server for biology · 2026Article
- scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies.Nature communications · 2026Article
- Cellular heterogeneity and multicellular mechanisms in the pathogenesis of late-life depression: insights from single-cell and spatial multi-omics.Frontiers in immunology · 2026Review
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- Review
- Exploring the mechanism of methyl parathion and its degradation product on depression through network toxicology and molecular docking.Scientific reports · 2025Article
- Transcriptomic Insights into Late-Life Depression and the Role of Environmental Drinking Water Composition: A Study on 18-Month-Old Mice.International journal of molecular sciences · 2025Article
- Automated image segmentation uncovers the role of CD74 high human microglia in cognitive decline.Research square · 2025Article
- Elevated NEGR1 in brain induces anxiety or depression-like phenotypes and synaptic dysfunction.Molecular psychiatry · 2025Article
- Analysis of Genomic and Transcriptomic Data Revealed Key Genes and Processes in the Development of Major Depressive Disorder.International journal of molecular sciences · 2025Article
- scTWAS: A powerful statistical framework for single-cell transcriptome-wide association studies.Research square · 2025Article
- Leveraging multiomic approaches to elucidate mechanisms of heterogeneity in Alzheimer's disease: Neuropsychiatric symptoms, co-pathologies, and sex differences.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Canonical and non-canonical roles of oligodendrocyte precursor cells in mental disorders.Npj mental health research · 2025Review
- Shared genetic architecture of gastroesophageal reflux disease and age related phenotypes.Scientific reports · 2025Article
- A Transcriptomic Signature of Depressive Symptoms in Late Life.Biological psychiatry global open science · 2025Article
- A Multi-omic study integrating plasma protein, multiple tissues, and single-cell identifies RNASET2 as a key gene for lung cancer.Discover oncology · 2025Article
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11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDepression, a common psychiatric illness and global public health problem, remains poorly understood across different life stages, which hampers the development of novel treatments.
methodsTo identify new candidate genes for therapeutic development, we performed differential gene expression analysis of single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of older adults (n = 424) in relation to antemortem depressive symptoms. Additionally, we integrated genome-wide association study results for depression (n = 500,199) along with genetic tools for inferring the expression of 14,048 unique genes in 7 cell types and 52 cell subtypes to perform a transcriptome-wide association study of depression followed by Mendelian randomization.
resultsOur single-nucleus transcriptome-wide association study analysis identified 68 candidate genes for depression and showed the greatest number being in excitatory and inhibitory neurons. Of the 68 genes, 53 were novel compared to previous studies. Notably, gene expression in different neuronal subtypes had varying effects on depression risk. Traits with high genetic correlations with depression, such as neuroticism, shared more transcriptome-wide association study genes than traits that were not highly correlated with depression. Complementing these analyses, differential gene expression analysis across 52 neocortical cell subtypes showed that genes such as KCNN2, SCAI, WASF3, and SOCS6 were associated with late-life depressive symptoms in specific cell subtypes.
conclusionsThese 2 sets of analyses illustrate the utility of large single-nucleus RNA sequencing data both to uncover genes whose expression is altered in specific cell subtypes in the context of depressive symptoms and to enhance the interpretation of well-powered genome-wide association studies so that we can prioritize specific susceptibility genes for further analysis and therapeutic development.
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