Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Multiple Allele Traits01:49

Multiple Allele Traits

The Concept of Multiple Allelism
Multiple Allele Traits01:49

Multiple Allele Traits

The Concept of Multiple Allelism
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

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.
GWAS does not require the identification of the target gene involved in...
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%...
Genetic Variation01:25

Genetic Variation

Genetic variation is the diversity in DNA sequences found among individuals of the same species. This diversity is crucial for a species' survival because it helps organisms adapt to environmental changes. Genetic variation begins with fertilization, where an egg and sperm cell merge. Each of these cells carries 23 chromosomes, up to 46 in the fertilized egg. Chromosomes are long DNA strands that contain genes, the basic units of heredity.
Genes exist in different versions called alleles, which...
X-linked Traits01:19

X-linked Traits

In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.

Nature communications·2024
Same author

Transcriptional Variabilities in Human hiPSC-derived Cardiomyocytes: All Genes Are Not Equal and Their Robustness May Foretell Donor's Disease Susceptibility.

bioRxiv : the preprint server for biology·2024
Same author

Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association.

Circulation·2024
Same author

The American Heart Association at 100: A Century of Scientific Progress and the Future of Cardiovascular Science: A Presidential Advisory From the American Heart Association.

Circulation·2024
Same author

Factors associated with frequency of fruit and vegetable consumption among selected sub-Saharan African populations: evidence from the Cardiovascular H3Africa Innovation Resource Project.

International journal of epidemiology·2024
Same author

Whole genome sequence analysis of apparent treatment resistant hypertension status in participants from the Trans-Omics for Precision Medicine program.

Frontiers in genetics·2024

Related Experiment Video

Updated: May 30, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
14:06

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER

Published on: June 23, 2012

A data-driven method for identifying rare variants with heterogeneous trait effects.

Qunyuan Zhang1, Marguerite R Irvin, Donna K Arnett

  • 1Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63108, USA. qunyuan@wustl.edu

Genetic Epidemiology
|August 6, 2011
PubMed
Summary
This summary is machine-generated.

We developed a new method, the P-value Weighted Sum Test (PWST), to improve rare variant association analysis. PWST enhances statistical power when variants have mixed effects on traits, outperforming direct collapsing methods.

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

Related Experiment Videos

Last Updated: May 30, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
14:06

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER

Published on: June 23, 2012

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
05:53

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Published on: June 21, 2018

Area of Science:

  • Genetics
  • Statistical Genetics
  • Bioinformatics

Background:

  • Rare variant association analysis is crucial for understanding complex traits.
  • Direct collapsing methods can lose power with heterogeneous variant effects, especially for quantitative traits.
  • Existing methods struggle with mixed positive and negative variant effects.

Purpose of the Study:

  • To propose a novel, data-driven method, the P-value Weighted Sum Test (PWST), for rare variant association analysis.
  • To address the limitations of direct collapsing when dealing with heterogeneous variant effects.
  • To increase statistical power in rare variant association studies.

Main Methods:

  • Developed the P-value Weighted Sum Test (PWST) using individual variant significance and effect direction.
  • Calculated a weighted sum score based on rescaled left-tail P-values.
  • Performed permutation tests to assess association between the score and the trait.
  • Evaluated PWST performance using simulations under various sampling strategies.

Main Results:

  • PWST significantly increases statistical power when variants exhibit heterogeneous effects.
  • The method is effective across different sampling strategies (random and extreme-tail sampling).
  • PWST successfully detected the collective effect of peroxisome proliferator-activated receptor alpha (PPARα) variants on triglyceride response in a real-world dataset.

Conclusions:

  • PWST offers a powerful and flexible approach for rare variant association analysis, particularly when variant effects are mixed.
  • The method improves upon traditional collapsing techniques by accounting for effect heterogeneity.
  • PWST has practical applications in genetic studies, such as analyzing gene-environment interactions and complex trait associations.