Dataset Information

Experimental Biology for the Identification of Causal Pathways in Atherosclerosis.

ABSTRACT: More than 60 genomic loci have been implicated by genome-wide association studies (GWAS) and exome-wide association studies as conferring an increased risk of myocardial infarction and coronary artery disease (CAD). However, the causal gene and variant is often unclear. Using the functional analysis of genetic variants in experimental animal models, we anticipate understanding which candidate gene at a specific locus is associated with atherosclerosis and revealing the underlying molecular and cellular mechanisms, ultimately leading to the identification of causal pathways in atherosclerosis and may provide novel therapeutic targets for the treatment of atherosclerotic cardiovascular disease.

SUBMITTER: Guo Y

PROVIDER: S-EPMC7088260 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Experimental Biology for the Identification of Causal Pathways in Atherosclerosis.

Guo Yanhong Y Garcia-Barrio Minerva T MT Wang Laiyuan L Chen Y Eugene YE

Cardiovascular drugs and therapy 20160201 1

More than 60 genomic loci have been implicated by genome-wide association studies (GWAS) and exome-wide association studies as conferring an increased risk of myocardial infarction and coronary artery disease (CAD). However, the causal gene and variant is often unclear. Using the functional analysis of genetic variants in experimental animal models, we anticipate understanding which candidate gene at a specific locus is associated with atherosclerosis and revealing the underlying molecular and c ...[more]

PMID: 26847647

Similar Datasets

Project description:BackgroundGenome-wide association studies (GWAS) have successfully identified genetic susceptible variants for complex diseases. However, the underlying mechanism of such association remains largely unknown. Most disease-associated genetic variants have been shown to reside in noncoding regions, leading to the hypothesis that regulation of gene expression may be the primary biological mechanism. Current methods to characterize gene expression mediating the effect of genetic variant on diseases, often analyzed one gene at a time and ignored the network structure. The impact of genetic variant can propagate to other genes along the links in the network, then to the final disease. There could be multiple pathways from the genetic variant to the final disease, with each having the chain structure since the first node is one specific SNP (Single Nucleotide Polymorphism) variant and the end is disease outcome. One key but inadequately addressed question is how to measure the between-node connection strength and rank the effects of such chain-type pathways, which can provide statistical evidence to give the priority of some pathways for potential drug development in a cost-effective manner.ResultsWe first introduce the maximal correlation coefficient (MCC) to represent the between-node connection, and then integrate MCC with K shortest paths algorithm to rank and identify the potential pathways from genetic variant to disease. The pathway importance score (PIS) was further provided to quantify the importance of each pathway. We termed this method as "MCC-SP". Various simulations are conducted to illustrate MCC is a better measurement of the between-node connection strength than other quantities including Pearson correlation, Spearman correlation, distance correlation, mutual information, and maximal information coefficient. Finally, we applied MCC-SP to analyze one real dataset from the Religious Orders Study and the Memory and Aging Project, and successfully detected 2 typical pathways from APOE genotype to Alzheimer's disease (AD) through gene expression enriched in Alzheimer's disease pathway.ConclusionsMCC-SP has powerful and robust performance in identifying the pathway(s) from the genetic variant to the disease. The source code of MCC-SP is freely available at GitHub ( https://github.com/zhuyuchen95/ADnet ).

Dataset Information

Experimental Biology for the Identification of Causal Pathways in Atherosclerosis.

Publications

Experimental Biology for the Identification of Causal Pathways in Atherosclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure