ArticleMolecular psychiatry2009
Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder.
Article in Molecular psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- A Systematic Review of the Human Accelerated Regions in Schizophrenia and Related Disorders: Where the Evolutionary and Neurodevelopmental Hypotheses Converge.International journal of molecular sciences · 2023Pooled it
- Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk.Progress in neuro-psychopharmacology & biological psychiatry · 2019Pooled it
- The effect of human-specific genetic variants on neuronal spinogenesis.Frontiers in genetics · 2026Review
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences.Molecular biology and evolution · 2024Article
- Article
- Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation.Journal of personalized medicine · 2021Article
- Identification of genetic overlap and novel risk loci for attention-deficit/hyperactivity disorder and bipolar disorder.Molecular psychiatry · 2021Article
- Investigation of genetic loci shared between bipolar disorder and risk-taking propensity: potential implications for pharmacological interventions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Genetic Mechanisms Underlying Cortical Evolution in Mammals.Frontiers in cell and developmental biology · 2021Review
- Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder.Molecular psychiatry · 2019Article
- Genetic pleiotropy between mood disorders, metabolic, and endocrine traits in a multigenerational pedigree.Translational psychiatry · 2018Article
- Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP).Translational psychiatry · 2018Article
- PREDICTD PaRallel Epigenomics Data Imputation with Cloud-based Tensor Decomposition.Nature communications · 2018Article
- Human Accelerated Regions and Other Human-Specific Sequence Variations in the Context of Evolution and Their Relevance for Brain Development.Genome biology and evolution · 2018Review
- Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.Schizophrenia bulletin · 2017Article
- Neuronal PAS Domain Proteins 1 and 3 Are Master Regulators of Neuropsychiatric Risk Genes.Biological psychiatry · 2017Article
- Associating transcription factors and conserved RNA structures with gene regulation in the human brain.Scientific reports · 2017Article
- Structural characterization of mammalian bHLH-PAS transcription factors.Current opinion in structural biology · 2017Review
- Individual differences in circadian locomotor parameters correlate with anxiety- and depression-like behavior.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The neuronal PAS domain 3 (NPAS3) gene encodes a neuronal transcription factor that is implicated in psychiatric disorders by the identification of a human chromosomal translocation associated with schizophrenia and a mouse knockout model with behavioural and hippocampal neurogenesis defects. To determine its contribution to the risk of psychiatric illness in the general population, we genotyped 70 single-nucleotide polymorphisms across the NPAS3 gene in 368 individuals with bipolar disorder, 386 individuals with schizophrenia and 455 controls. Modestly significant single-marker and global and individual haplotypes were identified in four discrete regions of the gene. The presence of both risk and protective haplotypes at each of these four regions indicated locus and allelic heterogeneity within NPAS3 and suggested a model whereby interactions between variants across the gene might contribute to susceptibility to illness. This was supported by predicting the most likely haplotype for each individual at each associated region and then calculating an NPAS3-mediated 'net genetic load' value. This value differed significantly from controls for both bipolar disorder (P=0.0000010) and schizophrenia (P=0.0000012). Logistic regression analysis also confirmed the combinatorial action of the four associated regions on disease risk. In addition, sensitivity/specificity plots showed that the extremes of the genetic loading distribution possess the greatest predictive power-a feature suggesting multiplicative allele interaction. These data add to recent evidence that the combinatorial analysis of a number of relatively small effect size haplotypes may have significant power to predict an individual's risk of a complex genetic disorder such as psychiatric illness.
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