ArticleMolecular psychiatry2020
Regulatory mechanisms of major depressive disorder risk variants.
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 37 papers, 3 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression.Nature human behaviour · 2025Pooled it
- Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.Nature human behaviour · 2024Pooled it
- A Systematic Review of Circulatory microRNAs in Major Depressive Disorder: Potential Biomarkers for Disease Prognosis.International journal of molecular sciences · 2022Pooled it
- Standardized chronic restraint stress protocols reveal dynamic evolution of behavioral adaptations in male mice: implications for translational neuroscience.Molecular psychiatry · 2026Article
- A multi-tissue mendelian randomization method based on eQTL data for mapping tissue-specific disease genes.BMC bioinformatics · 2026Article
- Elevated NEGR1 in brain induces anxiety or depression-like phenotypes and synaptic dysfunction.Molecular psychiatry · 2025Article
- The Single Nucleotide Substitution T → A rs2072580 Damages the CREB1 Binding Site in the BidirectionalGenes · 2025Article
- The regulatory variant rs1950834 confers the risk of depressive disorder by reducing LRFN5 expression.BMC medicine · 2025Article
- Genetic regulation of lncRNA expression in whole human brain and their contribution to CNS disorders.Briefings in bioinformatics · 2025Article
- Identification of Schizophrenia-Risk Regulatory Variant rs1399178 in the Non-coding Region With Its Impact on NRF1 Binding.CNS neuroscience & therapeutics · 2025Article
- Effects of Physical Activity on Disordered Eating Behaviours in Individuals With a Psychotic Disorder.Early intervention in psychiatry · 2025Article
- Gain of bipolar disorder-related lncRNA AP1AR-DT in mice induces depressive and anxiety-like behaviors by reducing Negr1-mediated excitatory synaptic transmission.BMC medicine · 2024Article
- LncRNA NPTN-IT1-201 Ameliorates Depressive-like Behavior by Targeting miR-142-5p and Regulating Inflammation and Apoptosis via BDNF.Current medical science · 2024Article
- Classification of MDD using a Transformer classifier with large-scale multisite resting-state fMRI data.Human brain mapping · 2024Article
- Disentangling the complexity of psoriasis in the post-genome-wide association era.Genes and immunity · 2023Review
- Review
- Sex Significantly Impacts the Function of Major Depression-Linked Variants In Vivo.Biological psychiatry · 2023Article
- Vector enabled CRISPR gene editing - A revolutionary strategy for targeting the diversity of brain pathologies.Coordination chemistry reviews · 2023Article
- The Wicked Relationship between Depression and Metabolic Syndrome.Clinical neuropsychiatry · 2023Review
- Association Between Single Nucleotide Polymorphisms Within lncRNA NONHSAT102891 and Depression Susceptibility in a Chinese Population.Neuropsychiatric disease and treatment · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders and a leading cause of disability worldwide. Though recent genome-wide association studies (GWAS) have identified multiple risk variants for MDD, how these variants confer MDD risk remains largely unknown. Here we systematically characterize the regulatory mechanism of MDD risk variants using a functional genomics approach. By integrating chromatin immunoprecipitation sequencing (ChIP-Seq) (from human brain tissues or neuronal cells) and position weight matrix (PWM) data, we identified 34 MDD risk SNPs that disrupt the binding of 15 transcription factors (TFs). We verified the regulatory effect of the TF binding-disrupting SNPs with reporter gene assays, allelic-specific expression analysis, and CRISPR-Cas9-mediated genome editing. Expression quantitative trait loci (eQTL) analysis identified the target genes that might be regulated by these regulatory risk SNPs. Finally, we found that NEGR1 (regulated by the TF binding-disrupting MDD risk SNP rs3101339) was dysregulated in the brains of MDD cases compared with controls, implying that rs3101339 may confer MDD risk by affecting NEGR1 expression. Our findings reveal how genetic variants contribute to MDD risk by affecting TF binding and gene regulation. More importantly, our study identifies the potential MDD causal variants and their target genes, thus providing pivotal candidates for future mechanistic study and drug development.
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