ArticleHuman molecular genetics2008
Variants in the estrogen receptor alpha gene and its mRNA contribute to risk for schizophrenia.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 149 citations in OpenAlex.
- Selective Estrogen Receptor Modulation Increases Hippocampal Activity during Probabilistic Association Learning in Schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Trial
- Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia.Molecular psychiatry · 2015Trial
- Exon 7 splicing of ERα predicts poor prognosis and increases phenotypic heterogeneity in luminal a subtype breast cancer.FEBS open bio · 2026Article
- Estrogen Receptor Gene 1 (Biology · 2023Article
- Metabolic Syndrome, BMI, and Polymorphism of Estrogen Receptor-α in Peri- and Post-Menopausal Polish Women.Metabolites · 2022Article
- Estrogens in schizophrenia: progress, current challenges and opportunities.Current opinion in psychiatry · 2021Review
- Review
- The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders.International journal of molecular sciences · 2020Review
- The effects of early life stress on motivated behaviors: A role for gonadal hormones.Neuroscience and biobehavioral reviews · 2020Review
- Raloxifene augmentation in men and women with a schizophrenia spectrum disorder: A study protocol.Contemporary clinical trials communications · 2020Article
- Article
- Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence.Sexual medicine · 2020Article
- Genetic Intersections of Language and Neuropsychiatric Conditions.Current psychiatry reports · 2020Review
- Sex-Specific Associations of Androgen Receptor CAG Trinucleotide Repeat Length and of Raloxifene Treatment with Testosterone Levels and Perceived Stress in Schizophrenia.Molecular neuropsychiatry · 2019Article
- Highly Variable Expression ofJournal of molecular and genetic medicine : an international journal of biomedical research · 2019Article
- Nuclear Receptors and Neuroinflammation in Schizophrenia.Molecular neuropsychiatry · 2018Article
- Review
- Protein-Protein Interaction Analysis of Common Top Genes in Obsessive-Compulsive Disorder (OCD) and Schizophrenia: Towards New Drug Approach Obsessive-Compulsive disorder (OCD) and Schizophrenia Comorbidity Gene Analysis.Iranian journal of pharmaceutical research : IJPR · 2018Article
- Serum levels of GPER-1 in euthymic bipolar patients.Neuropsychiatric disease and treatment · 2018Article
- Polymorphisms in sex steroid receptors: From gene sequence to behavior.Frontiers in neuroendocrinology · 2017Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Estrogen modifies human emotion and cognition and impacts symptoms of schizophrenia. We hypothesized that the variation in the estrogen receptor alpha (ESR1) gene and cortical ESR1 mRNA is associated with schizophrenia. In a small case-control genetic association analysis of postmortem brain tissue, genotype CC (rs2234693) and haplotypes containing the C allele of a single-nucleotide polymorphism (SNP) in intron1 (PvuII) were more frequent in African American schizophrenics (P = 0.01-0.001). In a follow-up family-based association analysis, we found overtransmission of PvuII allele C and a PvuII C-containing haplotype (P = 0.01-0.03) to African American and Caucasian patients with schizophrenia. Schizophrenics with the 'at risk' PvuII genotype had lower ESR1 mRNA levels in the frontal cortex. Eighteen ESR1 splice variants and decreased frequencies of the wild-type ESR1 mRNA were detected in schizophrenia. In one patient, a unique ESR1 transcript with a genomic insert encoding a premature stop codon and a truncated ESR1 protein lacking most of the estrogen binding domain was the only transcript detected. Using a luciferase assay, we found that mRNA encoding a truncated ESR1 significantly attenuates gene expression at estrogen-response elements demonstrating a dominant negative function. An intron 6 SNP [rs2273207(G)] was associated with an ESR1 splice variant missing exon seven. The T allele of another intron 6 SNP was part of a 3' haplotype less common in schizophrenia [rs2273206(T), rs2273207(G), rs2228480(G)]. Thus, the variation in the ESR1 gene is associated with schizophrenia and the mechanism of this association may involve alternative gene regulation and transcript processing.
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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.