Article

A systematic method for mapping multiple loci: an application to construct a genetic network for rheumatoid arthritis.

Department of Bioinformatics, the First Clinical College, and the Bio-pharmaceutical Key Laboratory of Heilongjiang Province and State, Harbin Medical University, Harbin, PR China.
Gene (impact factor: 2.34). 02/2008; 408(1-2):104-11. DOI:10.1016/j.gene.2007.10.028 pp.104-11
Source: PubMed

ABSTRACT The advent of high-throughput single nucleotide polymorphisms (SNPs) omics technologies has brought tremendous genetic data. Systematic evaluation of the genome-wide SNPs is expected to provide breakthroughs in the understanding of complex diseases. In this study, we developed a new systematic method for mapping multiple loci and applied the proposed method to construct a genetic network for rheumatoid arthritis (RA) via analysis of 746 multiplex families genotyped with more than five thousands of genome-wide SNPs. We successfully identified 41 significant SNPs relevant to RA, 25 associated genes and a number of important SNP-SNP interactions (SNP patterns). Many findings (loci, genes and interactions) have experimental support from previous studies while novel findings may define unknown genetic pathways for this complex disease. Finally, we constructed a genetic network by integrating the results from this analysis with the rapidly accumulated knowledge in biomedical domains, which gave us a more detailed insight onto the RA etiology. The results suggest that the proposed systematic method is powerful when applied to genome-wide association studies. Integrating the analysis of high-throughput SNP data with knowledge-based SNP functional annotation offers a promising way to reversely engineer the underlying genetic networks for complex human diseases.

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    Article: Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.
    Wei Jiang, Xia Li, Shaoqi Rao, Lihong Wang, Lei Du, Chuanxing Li, Chao Wu, Hongzhi Wang, Yadong Wang, Baofeng Yang
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    BMC Systems Biology 09/2008; 2:72. · 3.15 Impact Factor
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Keywords

746 multiplex families genotyped
 
accumulated knowledge
 
biomedical domains
 
complex disease
 
complex diseases
 
complex human diseases
 
five thousands
 
genetic network
 
genome-wide association studies
 
high-throughput single nucleotide polymorphisms
 
high-throughput SNP data
 
integrating
 
knowledge-based SNP functional annotation
 
new systematic method
 
proposed method
 
proposed systematic method
 
RA etiology
 
SNP patterns
 
tremendous genetic data
 
underlying genetic networks