北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学精神卫生研究所  > 期刊论文
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

Files in This Item:

There are no files associated with this item.


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.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Kang, Guolian]'s Articles
[Yue, Weihua]'s Articles
[Zhang, Jifeng]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Kang, Guolian]‘s Articles
[Yue, Weihua]‘s Articles
[Zhang, Jifeng]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace