Related Experiment Video
Updated: Jul 7, 2026
05:53
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Integrative statistical genetics prioritizes candidate ASCVD susceptibility genes across tissues
Qin Liu1, Xiaodi Han2, Yue-Qing Hu3
1Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China.
Molecular Medicine (Cambridge, Mass.)
|July 5, 2026
Summary
This study identifies 14 genes linked to atherosclerotic cardiovascular disease (ASCVD) susceptibility, highlighting four key genes with tissue-specific roles in disease development. These findings advance understanding of ASCVD genetics and identify potential therapeutic targets.
Area of Science:
- Integrative Statistical Genetics
- Cardiovascular Disease Research
- Genomics and Transcriptomics
Background:
- Atherosclerotic cardiovascular disease (ASCVD) is a major global cause of mortality.
- The genetic underpinnings and mechanistic pathways of ASCVD require further elucidation.
Purpose of the Study:
- To identify genetic factors contributing to ASCVD susceptibility.
- To explore the functional mechanisms and tissue-specific roles of these genetic factors.
Main Methods:
- Applied genomic structural equation modeling (SEM) to large-scale GWAS data (approx. 3.8 million individuals).
- Utilized cross-tissue transcriptome-wide association study (TWAS) integrating ASCVD genetics with GTEx v8 gene expression data.
- Employed Mendelian randomization, colocalization, PheWAS, and structural predictions for gene prioritization and functional validation.
Main Results:
- Identified 14 genes robustly associated with ASCVD susceptibility, including ARVCF, GFPT1, NFU1, and USP39.
- Demonstrated tissue-specific effects for key genes (e.g., ARVCF in artery aorta, GFPT1 in heart atrial appendage).
- Linked identified genes to cellular processes including cell adhesion, metabolism, and RNA splicing, with potential immune involvement.
Conclusions:
- An integrative statistical genetics approach enhanced functional understanding of ASCVD genetics.
- Four prioritized genes show potential roles in ASCVD pathogenesis via tissue-specific mechanisms.
- Identified genes represent promising candidates for future research and therapeutic development in ASCVD.
Related Concept Videos
01:11Genome-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...
GWAS does not require the identification of the target gene involved in...
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:29Pharmacogenomics: 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...
01:18Polygenic 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...
01:18Polygenic 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...