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学科主题: 精神卫生
题名:
Two-stage designs to identify the effects of SNP combinations on complex diseases
作者: Kang, Guolian2; Yue, Weihua1; Zhang, Jifeng2; Huebner, Marianne3; Zhang, Handi1; Ruan, Yan1; Lu, Tianlan1; Ling, Yansu1; Zuo, Yijun3; Zhang, Dai1
关键词: SNP pattern ; synergistic block ; association study
刊名: JOURNAL OF HUMAN GENETICS
发表日期: 2008-08-01
DOI: 10.1007/s10038-008-0307-x
卷: 53, 期:8, 页:739-746
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
关键词[WOS]: MULTIFACTOR-DIMENSIONALITY REDUCTION ; DETECTING GENE-GENE ; BREAST-CANCER ; ASSOCIATION ; SCHIZOPHRENIA ; EPISTASIS
英文摘要:

The genetic basis of complex diseases is expected to be highly heterogeneous, with many disease genes, where each gene by itself has only a small effect. Based on the nonlinear contributions of disease genes across the genome to complex diseases, we introduce the concept of single nucleotide polymorphism (SNP) synergistic blocks. A two-stage approach is applied to detect the genetic association of synergistic blocks with a disease. In the first stage, synergistic blocks associated with a complex disease are identified by clustering SNP patterns and choosing blocks within a cluster that minimize a diversity criterion. In the second stage, a logistic regression model is given for a synergistic block. Using simulated case-control data, we demonstrate that our method has reasonable power to identify gene-gene interactions. To further evaluate the performance of our method, we apply our method to 17 loci of four candidate genes for paranoid schizophrenia in a Chinese population. Five synergistic blocks are found to be associated with schizophrenia, three of which are negatively associated (odds ratio, OR < 0.3, P < 0.05), while the others are positively associated (OR > 2.0, P < 0.05). The mathematical models of these five synergistic blocks are presented. The results suggest that there may be interactive effects for schizophrenia among variants of the genes neuregulin 1 (NRG1, 8p22-p11), G72 (13q34), the regulator of G-protein signaling-4 (RGS4, 1q21-q22) and frizzled 3 (FZD3, 8p21). Using synergistic blocks, we can reduce the dimensionality in a multi-locus association analysis, and evaluate the sizes of interactive effects among multiple disease genes on complex phenotypes.

语种: 英语
WOS记录号: WOS:000258112900008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62546
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Mental Hlth, Key Lab Mental Hlth, Minist Hlth, Beijing 100083, Peoples R China
2.Chinese Acad Sci, Acad Math & Syst Sci, Inst Syst Sci, Key Lab Syst & Control, Beijing 100080, Peoples R China
3.Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA

Recommended Citation:
Kang, Guolian,Yue, Weihua,Zhang, Jifeng,et al. Two-stage designs to identify the effects of SNP combinations on complex diseases[J]. JOURNAL OF HUMAN GENETICS,2008,53(8):739-746.
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