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Related Concept Videos

Polygenic Traits01:18

Polygenic Traits

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...
Polygenic Traits01:18

Polygenic Traits

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...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...

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  3. Comparing Pathway-informed Polygenic Risk Score Strategies: A Multi-cohort Evaluation Of Amyloid-β.
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  3. Comparing Pathway-informed Polygenic Risk Score Strategies: A Multi-cohort Evaluation Of Amyloid-β.

Related Experiment Video

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
09:38

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease

Published on: November 14, 2017

Comparing Pathway-Informed Polygenic Risk Score Strategies: A multi-cohort evaluation of Amyloid-β.

Xiyuan Zhang, Benjamin Goudey, Simon M Laws

    Medrxiv : the Preprint Server for Health Sciences
    |June 5, 2026

    View abstract on PubMed

    Summary
    This summary is machine-generated.

    Pathway-informed polygenic risk scores (PRS) improve prediction of brain amyloid-β positivity. Carefully curated pathways, especially literature-derived ones, enhance PRS accuracy beyond standard methods, offering clinical potential.

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    09:38

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    Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
    09:34

    Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

    Published on: April 4, 2018

    Area of Science:

    • Genetics
    • Neuroscience
    • Biomarkers

    Background:

    • Polygenic risk scores (PRS) are crucial for predicting complex disease risk.
    • Integrating biological pathway information into PRS construction can enhance predictive power.
    • Brain amyloid-β (Aβ) positivity is a key biomarker for Alzheimer's disease.

    Purpose of the Study:

    • To systematically evaluate different pathway-informed PRS strategies for predicting brain Aβ positivity.
    • To determine which methods best leverage biological annotations for improved risk prediction.
    • To compare pathway-derived PRS with standard PRS approaches and the APOE locus model.

    Main Methods:

    • Systematic benchmarking of PRS construction approaches integrating pathway information.
    • Utilized two cohorts: Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarkers and Lifestyle (AIBL).
  • Compared standard PRS (clumping and thresholding), pathway-guided SNP selection PRS, and pathway-specific PRS ensembles using machine learning (ML).

    • Main Results:

    • Pathway-informed PRS using literature-curated pathways significantly outperformed standard PRS and APOE locus models in predicting Aβ positivity (median AUC = 0.763).
    • This approach demonstrated enhanced ability to identify extreme risk subgroups.
    • Literature-curated pathways yielded better performance than broader database-derived pathways.

    Conclusions:

    • Pathway-informed PRS meaningfully improve genetic risk prediction for Aβ positivity.
    • Careful curation of pathway definitions is critical for optimal performance.
    • Literature-curated pathways offer practical guidance for constructing effective PRS in polygenic traits.