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Related Concept Videos

Polygenic Traits01:18

Polygenic Traits

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When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...
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Human Genetics01:28

Human Genetics

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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
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Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders01:27

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Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
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Genome-wide Association Studies-GWAS01:11

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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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Psychological and Sociocultural Causes of Schizophrenia01:29

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Schizophrenia, a complex psychiatric disorder, has been historically misunderstood. Early psychological theories attributed its origins to childhood trauma and unresponsive parenting. However, contemporary research largely rejects these notions, favoring the vulnerability-stress hypothesis. This model proposes that individuals with a genetic predisposition to schizophrenia may develop the disorder following exposure to significant environmental stressors. Notably, studies on high-risk...
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Epistasis Analysis01:09

Epistasis Analysis

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Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
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Related Experiment Video

Updated: Jul 19, 2025

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
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Psychosis Endophenotypes: A Gene-Set-Specific Polygenic Risk Score Analysis.

Baihan Wang1,2, Haritz Irizar1,3, Johan H Thygesen1,4

  • 1Department of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.

Schizophrenia Bulletin
|August 15, 2023
PubMed
Summary
This summary is machine-generated.

Genetic risk for schizophrenia is linked to reduced P300 brainwave amplitudes, suggesting early developmental impacts. Gene-set polygenic scores help uncover psychosis endophenotype mechanisms.

Keywords:
EEGP300bipolar disorderneurodevelopmentschizophrenia

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Endophenotypes offer a link between psychosis and genetic factors.
  • Understanding the biological mechanisms of endophenotypes is crucial but remains challenging.
  • This study investigates genetic contributions to psychosis endophenotypes.

Purpose of the Study:

  • To identify biological mechanisms underlying psychosis endophenotypes.
  • To partition polygenic risk scores into specific gene sets.
  • To test associations between gene-set-specific polygenic risk scores and endophenotypes.

Main Methods:

  • Calculated polygenic risk scores for schizophrenia and bipolar disorder using brain-related gene sets.
  • Generated 378 gene-set-specific polygenic risk scores for 4506 participants.
  • Assessed seven endophenotypes and used linear mixed-effects models to test associations.

Main Results:

  • A reduced P300 amplitude was significantly associated with higher schizophrenia polygenic risk scores in the forebrain regionalization gene set (P = 6 × 10-5).
  • The forebrain regionalization gene set explained more variance in P300 amplitude (R2 = 0.032) compared to genome-wide scores.
  • This highlights a specific genetic pathway influencing an observable endophenotype.

Conclusions:

  • Reduced P300 amplitudes may indicate that genetic variants impact early brain development, increasing schizophrenia risk.
  • Gene-set-specific polygenic risk scores are valuable for dissecting psychosis endophenotype mechanisms.
  • Findings provide a basis for experimental validation in cellular and animal models.