Novel association strategy with copy number variation for identifying new risk Loci of human diseases.
Novel association strategy with copy number variation for identifying new risk Loci of human diseases.
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DOI：
10.1371/journal.pone.0012185
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发表时间：
2010-08-20
期刊：
影响因子：
3.7
通讯作者：
Kong X
中科院分区：
文献类型：
--
作者：
Chen X;Li X;Wang P;Liu Y;Zhang Z;Zhao G;Xu H;Zhu J;Qin X;Chen S;Hu L;Kong X
Copy number variations (CNV) are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort. Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP) signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder. Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases.
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