Identifying disease related sub-pathways for analysis of genome-wide association studies |
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Authors: | Li Chunquan Han Junwei Shang Desi Li Jing Wang Yan Wang Yingying Zhang Yunpeng Yao Qianlan Zhang Chunlong Li Kongning Li Xia |
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Affiliation: | Harbin Medical University, Harbin, China. |
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Abstract: | Most methods for genome-wide association studies (GWAS) focus on discovering a single genetic variant, but the pathogenesis of complex diseases is thought to arise from the joint effect of multiple genetic variants. Information about pathway structure, such as the interactions and distances between gene products within pathways, can help us learn more about the functions and joint effect of genes associated with disease risk. We developed a novel sub-pathway based approach to study the joint effect of multiple genetic variants that are modestly associated with disease. The approach prioritized sub-pathways based on the significance values of single nucleotide polymorphisms (SNPs) and the interactions and distances between gene products within pathways. We applied the method to seven complex diseases. The result showed that our method can efficiently identify statistically significant sub-pathways associated with the pathogenesis of complex diseases. The approach identified sub-pathways that may inform the interpretation of GWAS data. |
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Keywords: | GWAS, genome-wide association studies SNPs, single-nucleotide polymorphisms RA, rheumatoid arthritis CD, Crohn's disease T1D, type 1 diabetes BD, bipolar disorder HT, hypertension CAD, coronary artery disease T2D, type 2 diabetes KEGG, Kyoto Encyclopedia of Genes and Genomes KOs, KEGG Orthology identifiers WTCCC, Wellcome Trust Case Control Consortium |
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