Novel Association Strategy with Copy Number Variation for Identifying New Risk Loci of Human Diseases

Xianfeng Chen, Xinlei Li, Ping Wang, Yang Liu, Zhenguo Zhang, Guoping Zhao, Haiming Xu, Jun Zhu, Xueying Qin, Suchao Chen, Landian Hu and Xiangyin Kong

PLOS ONE, 2010, vol. 5, issue 8, 1-10

Abstract: Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.

Date: 2010
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012185 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 12185&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0012185

DOI: 10.1371/journal.pone.0012185

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().