Systems-level analysis of genome-wide association data.
Systems-level analysis of genome-wide association data.
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DOI：
10.1534/g3.112.004788
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Farber CR
中科院分区：
文献类型：
--
作者：
Farber CR
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.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
影响因子：
4.3
作者：
Bratic, Ivana;Trifunovic, Aleksandra
通讯作者：
Trifunovic, Aleksandra
DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
Alter, O;Brown, PO;Botstein, D
通讯作者：
Botstein, D
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP