Searching Genome-Wide Multi-Locus Associations for Multiple Diseases Based on Bayesian Inference

被引:13
作者
Guo, Xuan [1 ]
Zhang, Jing [2 ]
Cai, Zhipeng [1 ]
Du, Ding-Zhu [3 ]
Pan, Yi [1 ]
机构
[1] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA
[2] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA
[3] Univ Texas Dallas, Dept Comp Sci, Richardson, TX 75080 USA
关键词
Bayesian inference; MCMC; genome-wide association studies; genetic factors; epistasis; EPISTATIC INTERACTION DETECTION; GENE-GENE INTERACTIONS; SELECTION;
D O I
10.1109/TCBB.2016.2527648
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Taking the advantage of high-throughput single nucleotide polymorphism ( SNP) genotyping technology, large genome-wide association studies (GWASs) have been considered to hold promise for unraveling complex relationships between genotypes and phenotypes. Current multi-locus-based methods are insufficient to detect interactions with diverse genetic effects on multifarious diseases. Also, statistic tests for high-order epistasis(>= 2 SNPs) raise huge computational and analytical challenges because the computation increases exponentially as the growth of the cardinality of SNPs combinations. In this paper, we provide a simple, fast and powerful method, named DAM, using Bayesian inference to detect genome-wide multi-locus epistatic interactions in multiple diseases. Experimental results on simulated data demonstrate that our method is powerful and efficient. We also apply DAM on two GWAS datasets from WTCCC, i.e., Rheumatoid Arthritis and Type 1 Diabetes, and identify some novel findings. Therefore, we believe that our method is suitable and efficient for the full-scale analysis of multi-disease-related interactions in GWASs.
引用
收藏
页码:600 / 610
页数:11
相关论文
共 35 条
[1]  
Bateson W., 1909, MENDELS PRINCIPLES H
[2]   Identifying Antigenicity-Associated Sites in Highly Pathogenic H5N1 Influenza Virus Hemagglutinin by Using Sparse Learning [J].
Cai, Zhipeng ;
Ducatez, Mariette F. ;
Yang, Jialiang ;
Zhang, Tong ;
Long, Li-Ping ;
Boon, Adrianus C. ;
Webby, Richard J. ;
Wan, Xiu-Feng .
JOURNAL OF MOLECULAR BIOLOGY, 2012, 422 (01) :145-155
[3]   Antigenic distance measurements for seasonal influenza vaccine selection [J].
Cai, Zhipeng ;
Zhang, Tong ;
Wan, Xiu-Feng .
VACCINE, 2012, 30 (02) :448-453
[4]   A Computational Framework for Influenza Antigenic Cartography [J].
Cai, Zhipeng ;
Zhang, Tong ;
Wan, Xiu-Feng .
PLOS COMPUTATIONAL BIOLOGY, 2010, 6 (10)
[5]   Most parsimonious haplotype allele sharing determination [J].
Cai Z. ;
Sabaa H. ;
Wang Y. ;
Goebel R. ;
Wang Z. ;
Xu J. ;
Stothard P. ;
Lin G. .
BMC Bioinform., 2009, 10 (1)
[6]   Efficient haplotype inference algorithms in one whole genome scan for pedigree data with non-genotyped founders [J].
Cheng, Yongxi ;
Sabaa, Hadi ;
Cai, Zhipeng ;
Goebel, Randy ;
Lin, Guohui .
ACTA MATHEMATICAE APPLICATAE SINICA-ENGLISH SERIES, 2009, 25 (03) :477-488
[7]   Detecting gene-gene interactions that underlie human diseases [J].
Cordell, Heather J. .
NATURE REVIEWS GENETICS, 2009, 10 (06) :392-404
[8]   Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans [J].
Cordell, HJ .
HUMAN MOLECULAR GENETICS, 2002, 11 (20) :2463-2468
[9]   Genome-Wide Interaction-Based Association of Human Diseases - A Survey [J].
Guo, Xuan ;
Yu, Ning ;
Gu, Feng ;
Ding, Xiaojun ;
Wang, Jianxin ;
Pan, Yi .
TSINGHUA SCIENCE AND TECHNOLOGY, 2014, 19 (06) :596-616
[10]   Cloud computing for detecting high-order genome-wide epistatic interaction via dynamic clustering [J].
Guo, Xuan ;
Meng, Yu ;
Yu, Ning ;
Pan, Yi .
BMC BIOINFORMATICS, 2014, 15