ArticlePLoS genetics2009
Adaptive variation regulates the expression of the human SGK1 gene in response to stress.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer.Cancer research · 2011Pooled it
- Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- miR-16-2-3p enhances glucocorticoid sensitivity in ulcerative colitis by targeting CREB1 and NF-κB1.Human cell · 2026Article
- Single-cell characterization of the adult male hippocampus suggests a prominent, and cell-type specific, role for Nrgn and Sgk1 in response to a social stressor.Molecular psychiatry · 2026Article
- Age-related microbiome metabolites alter RNA splicing and chromatin accessibility in the brain.bioRxiv : the preprint server for biology · 2025Article
- Genotype × environment interactions in gene regulation and complex traits.Nature genetics · 2024Review
- Emerging Role of Serum Glucocorticoid-Regulated Kinase 1 in Pathological Pain.Frontiers in molecular neuroscience · 2021Article
- The Emerging Role of SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) in Major Depressive Disorder: Hypothesis and Mechanisms.Frontiers in genetics · 2020Review
- Implication of Spiritual Network Support System in Epigenomic Modulation and Health Trajectory.International journal of environmental research and public health · 2019Review
- Region- and time-dependent gene regulation in the amygdala and anterior cingulate cortex of a PTSD-like mouse model.Molecular brain · 2019Article
- Leonurine promotes neurite outgrowth and neurotrophic activity by modulating the GR/SGK1 signaling pathway in cultured PC12 cells.Neuroreport · 2019Article
- Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Association ofFrontiers in genetics · 2019Article
- Vitamin D Regulation of the Uridine Phosphorylase 1 Gene and Uridine-Induced DNA Damage in Colon in African Americans and European Americans.Gastroenterology · 2018Article
- Article
- Dietary factors in rheumatic autoimmune diseases: a recipe for therapy?Nature reviews. Rheumatology · 2017Review
- SGK-1 protects kidney cells against apoptosis induced by ceramide and TNF-α.Cell death & disease · 2015Article
- Human social genomics.PLoS genetics · 2014Review
- Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response.The pharmacogenomics journal · 2013Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The Serum and Glucocorticoid-regulated Kinase1 (SGK1) gene is a target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining population genetics and molecular biology methods, we identified a variant (rs9493857) with marked allele frequency differences between populations of African and European ancestry and with a strong correlation between allele frequency and latitude in worldwide population samples. This SNP is located in a GR-binding region upstream of SGK1 that was identified using a GR ChIP-chip. SNP rs9493857 also lies within a predicted binding site for Oct1, a transcription factor known to cooperate with the GR in the transactivation of target genes. Using ChIP assays, we show that both GR and Oct1 bind to this region and that the ancestral allele at rs9493857 binds the GR-Oct1 complex more efficiently than the derived allele. Finally, using a reporter gene assay, we demonstrate that the ancestral allele is associated with increased glucocorticoid-dependent gene expression when compared to the derived allele. Our results suggest a novel paradigm in which hormonal responsiveness is modulated by sequence variation in the regulatory regions of nuclear receptor target genes. Identifying such functional variants may shed light on the mechanisms underlying inter-individual variation in response to environmental stressors and to hormonal therapy, as well as in the susceptibility to hormone-dependent diseases.
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Registered trials
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.