scholarly journals Systems-Level Analysis of Genome-Wide Association Data

2013 ◽  
Vol 3 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Charles R Farber
Keyword(s):  
Network Analysis ◽  
Genome Wide Association ◽  
Coexpression Network ◽  
Genome Wide Association Studies ◽  
Gene Coexpression Network ◽  
Mineral Density ◽  
Gene Coexpression ◽  
Genome Wide ◽  
Nominal Evidence ◽  
Level Analysis

Abstract Genome-wide association studies (GWAS) have emerged as the method of choice for identifying common variants affecting complex disease. In a GWAS, particular attention is placed, for obvious reasons, on single-nucleotide polymorphisms (SNPs) that exceed stringent genome-wide significance thresholds. However, it is expected that many SNPs with only nominal evidence of association (e.g., P < 0.05) truly influence disease. Efforts to extract additional biological information from entire GWAS datasets have primarily focused on pathway-enrichment analyses. However, these methods suffer from a number of limitations and typically fail to lead to testable hypotheses. To evaluate alternative approaches, we performed a systems-level analysis of GWAS data using weighted gene coexpression network analysis. A weighted gene coexpression network was generated for 1918 genes harboring SNPs that displayed nominal evidence of association (P ≤ 0.05) from a GWAS of bone mineral density (BMD) using microarray data on circulating monocytes isolated from individuals with extremely low or high BMD. Thirteen distinct gene modules were identified, each comprising coexpressed and highly interconnected GWAS genes. Through the characterization of module content and topology, we illustrate how network analysis can be used to discover disease-associated subnetworks and characterize novel interactions for genes with a known role in the regulation of BMD. In addition, we provide evidence that network metrics can be used as a prioritizing tool when selecting genes and SNPs for replication studies. Our results highlight the advantages of using systems-level strategies to add value to and inform GWAS.

scholarly journals Genome-Wide Association Studies Based on Equine Joint Angle Measurements Reveal New QTL Affecting the Conformation of Horses

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 370 ◽  
Author(s):  
Annik Imogen Gmel ◽  
Thomas Druml ◽  
Rudolf von Niederhäusern ◽  
Tosso Leeb ◽  
Markus Neuditschko
Keyword(s):  
Joint Angle ◽  
Association Studies ◽  
Genome Wide Association ◽  
Cranial Morphology ◽  
Genome Wide Association Studies ◽  
Joint Angles ◽  
Mineral Density ◽  
Mixed Effect ◽  
Stifle Joint ◽  
Genome Wide

The evaluation of conformation traits is an important part of selection for breeding stallions and mares. Some of these judged conformation traits involve joint angles that are associated with performance, health, and longevity. To improve our understanding of the genetic background of joint angles in horses, we have objectively measured the angles of the poll, elbow, carpal, fetlock (front and hind), hip, stifle, and hock joints based on one photograph of each of the 300 Franches-Montagnes (FM) and 224 Lipizzan (LIP) horses. After quality control, genome-wide association studies (GWASs) for these traits were performed on 495 horses, using 374,070 genome-wide single nucleotide polymorphisms (SNPs) in a mixed-effect model. We identified two significant quantitative trait loci (QTL) for the poll angle on ECA28 (p = 1.36 × 10−7), 50 kb downstream of the ALX1 gene, involved in cranial morphology, and for the elbow joint on ECA29 (p = 1.69 × 10−7), 49 kb downstream of the RSU1 gene, and 75 kb upstream of the PTER gene. Both genes are associated with bone mineral density in humans. Furthermore, we identified other suggestive QTL associated with the stifle joint on ECA8 (p = 3.10 × 10−7); the poll on ECA1 (p = 6.83 × 10−7); the fetlock joint of the hind limb on ECA27 (p = 5.42 × 10−7); and the carpal joint angle on ECA3 (p = 6.24 × 10−7), ECA4 (p = 6.07 × 10−7), and ECA7 (p = 8.83 × 10−7). The application of angular measurements in genetic studies may increase our understanding of the underlying genetic effects of important traits in equine breeding.

scholarly journals Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis

2019 ◽  
Vol 49 (10) ◽  
pp. 1195-1206 ◽  
Author(s):  
Aiping Tian ◽  
Ke Pu ◽  
Boxuan Li ◽  
Min Li ◽  
Xiaoguang Liu ◽  
...  
Keyword(s):  
Network Analysis ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Gene Coexpression ◽  
Coexpression Network Analysis

scholarly journals Correction to: Weighted gene coexpression network analysis-based identification of key modules and hub genes associated with drought sensitivity in rice

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Baiyang Yu ◽  
Jianbin Liu ◽  
Di Wu ◽  
Ying Liu ◽  
Weijian Cen ◽  
...  
Keyword(s):  
Network Analysis ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Hub Genes ◽  
Drought Sensitivity ◽  
Gene Coexpression ◽  
Coexpression Network Analysis

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Identification of Candidate Genes and MicroRNAs for Acute Myocardial Infarction by Weighted Gene Coexpression Network Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yan Li ◽  
Xiao_nan He ◽  
Chao Li ◽  
Ling Gong ◽  
Min Liu
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Microarray Data ◽  
Differentially Expressed ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Gene Coexpression ◽  
Coexpression Network Analysis

Background. Identification of potential molecular targets of acute myocardial infarction is crucial to our comprehensive understanding of the disease mechanism. However, studies of gene coexpression analysis via jointing multiple microarray data of acute myocardial infarction still remain restricted. Methods. Microarray data of acute myocardial infarction (GSE48060, GSE66360, GSE97320, and GSE19339) were downloaded from Gene Expression Omnibus database. Three data sets without heterogeneity (GSE48060, GSE66360, and GSE97320) were subjected to differential expression analysis using MetaDE package. Differentially expressed genes having upper 25% variation across samples were imported in weighted gene coexpression network analysis. Functional and pathway enrichment analyses were conducted for genes in the most significant module using DAVID. The predicted microRNAs to regulate target genes in the most significant module were identified using TargetScan. Moreover, subpathway analyses using iSubpathwayMiner package and GenCLiP 2.0 were performed on hub genes with high connective weight in the most significant module. Results. A total of 1027 differentially expressed genes and 33 specific modules were screened out between acute myocardial infarction patients and control samples. Ficolin (collagen/fibrinogen domain containing) 1 (FCN1), CD14 molecule (CD14), S100 calcium binding protein A9 (S100A9), and mitochondrial aldehyde dehydrogenase 2 (ALDH2) were identified as critical target molecules; hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential regulators of the expression of the key genes in the two biggest modules. Conclusions. FCN1, CD14, S100A9, ALDH2, hsa-let-7d, hsa-let-7b, hsa-miR-124-3, and hsa-miR-9-1 were identified as potential candidate regulators in acute myocardial infarction. These findings might provide new comprehension into the underlying molecular mechanism of disease.

Early Stage Biomarkers Screening of Prostate Cancer Based on Weighted Gene Coexpression Network Analysis

2019 ◽  
Vol 38 (5) ◽  
pp. 468-475 ◽  
Author(s):  
Lingyin Meng ◽  
Yang Li ◽  
Jing Ren ◽  
Tao Shi ◽  
Jianlong Men ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Network Analysis ◽  
Early Stage ◽  
Coexpression Network ◽  
Gene Coexpression Network ◽  
Gene Coexpression ◽  
Coexpression Network Analysis
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