ArticleProceedings of the National Academy of Sciences of the United States of America2023
High-throughput screening of glucocorticoid-induced enhancer activity reveals mechanisms of stress-related psychiatric disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The predictive value of polygenic risk scores for depression in gene-environment interaction studies: a systematic review.Translational psychiatry · 2026Pooled it
- Article
- A cell line-derived, immune-competent neurospheroid model to study neuroinflammation and human brain disorders.Frontiers in immunology · 2026Article
- Genetic Evidence Supporting a Role for Brain Region Volume and Functional Network Alterations in Major Depression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Astrocytic glutamate regulation is shaped by adversity and glucocorticoid signalling.bioRxiv : the preprint server for biology · 2025Article
- Stress Molecular Signaling in Interaction With Cognition.Biological psychiatry · 2025Review
- Just a SNP away: The future ofCell insight · 2025Review
- Endophenotype 2.0: updated definitions and criteria for endophenotypes of psychiatric disorders, incorporating new technologies and findings.Translational psychiatry · 2024Review
- Exposure to elevated glucocorticoid during development primes altered transcriptional responses to acute stress in adulthood.iScience · 2024Article
- Translation of genome-wide association study: from genomic signals to biological insights.Frontiers in genetics · 2024Review
- The neurobiology of stress: Vulnerability, resilience, and major depression.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure to stressful life events increases the risk for psychiatric disorders. Mechanistic insight into the genetic factors moderating the impact of stress can increase our understanding of disease processes. Here, we test 3,662 single nucleotide polymorphisms (SNPs) from preselected expression quantitative trait loci in massively parallel reporter assays to identify genetic variants that modulate the activity of regulatory elements sensitive to glucocorticoids, important mediators of the stress response. Of the tested SNP sequences, 547 were located in glucocorticoid-responsive regulatory elements of which 233 showed allele-dependent activity. Transcripts regulated by these functional variants were enriched for those differentially expressed in psychiatric disorders in the postmortem brain. Phenome-wide Mendelian randomization analysis in 4,439 phenotypes revealed potentially causal associations specifically in neurobehavioral traits, including major depression and other psychiatric disorders. Finally, a functional gene score derived from these variants was significantly associated with differences in the physiological stress response, suggesting that these variants may alter disease risk by moderating the individual set point of the stress response.
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