Related Experiment Video
Updated: Jul 1, 2025
05:01
A Pathway Association Study Tool for GWAS Analyses of Metabolic Pathway Information
Published on: July 1, 2020
3.3K
Inferring a directed acyclic graph of phenotypes from GWAS summary statistics
Rachel Zilinskas1, Chunlin Li2, Xiaotong Shen3
1Statistics and Data Corporation, Tempe, AZ 85288, United States.
Biometrics
|March 12, 2024
Summary
This study introduces a new computational biology method to build phenotype networks using genetic data and summary statistics. The approach aids in understanding disease causes, like linking cardiovascular proteins to Alzheimer's disease.
Area of Science:
- Computational biology
- Genetics
- Network analysis
Background:
- Phenotype network estimation is crucial for understanding disease etiology.
- Existing methods may require individual-level genetic data.
Purpose of the Study:
- To present a novel method for constructing phenotype networks using summary statistics from genome-wide association studies (GWAS).
- To enable causal inference on directed edges within these networks.
Main Methods:
- Utilizes a Gaussian linear structure model with a directed acyclic graph (DAG).
- Employs genetic variants as instrumental variables.
- Requires only GWAS summary statistics and reference genotype data.
Main Results:
- Successfully estimated a causal network of 29 cardiovascular-related proteins.
- Linked the cardiovascular protein network to Alzheimer's disease (AD).
- Simulation studies confirmed the method's effectiveness.
Conclusions:
- The developed method provides an efficient way to estimate phenotype networks from summary statistics.
- Facilitates the study of complex disease relationships, such as cardiovascular factors and AD.
- An R package (sumdag) and Shiny application are available for public use.
Keywords:
Alzheimer’s disease (AD)directed acyclic graph (DAG)genome-wide association study (GWAS)likelihood ratio testproteomicsMore Related Videos
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
13.4K
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...
GWAS does not require the identification of the target gene involved in...
13.4K
01:35Pedigree Analysis
84.2K
Overview
84.2K
01:18Polygenic Traits
65.8K
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...
65.8K
02:27Background and Environment Affect Phenotype
6.5K
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
6.5K
01:43Incomplete Dominance
22.6K
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
22.6K
02:46Genetic Screens
4.9K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
4.9K