title: A multilocus linkage disequilibrium measure based on mutual information theory and its applications.
abstract: Evaluating the patterns of linkage disequilibrium (LD) is important for association mapping study as well as for studying the genomic architecture of human genome (e.g., haplotype block structures). Commonly used bi-allelic pairwise measures for assessing LD between two loci, such as r(2) and D', may not make full and efficient use of modern multilocus data. Though extended to multilocus scenarios, their performance is still questionable. Meanwhile, most existing measures for an entire multilocus region, such as normalized entropy difference, do not consider existence of LD heterogeneity across the region under investigation. Additionally, these existing multilocus measures cannot handle distant regions where long-range LD patterns may exist. In this study, we proposed a novel multilocus LD measure developed based on mutual information theory. Our proposed measure described LD pattern between two chromosome regions each of which may consist of multiple loci (including multi-allele loci). As such, the proposed measure can better characterize LD patterns between two arbitrary regions. As potential applications, we developed algorithms on the proposed measure for partitioning haplotype blocks and for selecting haplotype tagging SNPs (htSNPs), which were helpful for follow-up association tests. The results on both simulated and empirical data showed that our LD measure had distinct advantages over pairwise and other multilocus measures. First, our measure was more robust, and can capture comprehensively the LD information between neighboring as well as disjointed regions. Second, haplotype blocks were better described via our proposed measure. Furthermore, association tests with htSNPs from the proposed algorithm had improved power over tests on single markers and on haplotypes.
authors.affiliation: Institute of Molecular Genetics and the Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, 710049, Xi'an, Shaanxi, People's Republic of China. zlbio12@gmail.com
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000465:Algorithms; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide
references.citation: Am J Hum Genet. 2002 Nov;71(5):1227-34
references.pmid: 12384857
references.citation: Science. 2002 Jun 21;296(5576):2225-9
references.pmid: 12029063
references.citation: Nat Rev Genet. 2002 Apr;3(4):299-309
references.pmid: 11967554
references.citation: Am J Hum Genet. 1994 Apr;54(4):705-14
references.pmid: 8128969
references.citation: Mol Biol Evol. 1995 Sep;12(5):921-7
references.pmid: 7476138
references.citation: PLoS Genet. 2006 Jul;2(7):e121
references.pmid: 16895449
references.citation: Nature. 2001 May 10;411(6834):199-204
references.pmid: 11346797
references.citation: Genetics. 2001 Jan;157(1):413-23
references.pmid: 11139521
references.citation: Am J Hum Genet. 2007 Apr;80(4):705-15
references.pmid: 17357076
references.citation: Hum Mol Genet. 2003 Apr 1;12(7):771-6
references.pmid: 12651872
references.citation: Genome Res. 2000 Oct;10(10):1435-44
references.pmid: 11042143
references.citation: Bioinformatics. 2002;18 Suppl 2:S231-40
references.pmid: 12386007
references.citation: Ann Hum Genet. 1999 Mar;63(Pt 2):167-79
references.pmid: 10738528
references.citation: Genetics. 1964 Jan;49(1):49-67
references.pmid: 17248194
references.citation: Genet Epidemiol. 2005 Apr;28(3):193-206
references.pmid: 15637716
references.citation: Am J Hum Genet. 2002 Dec;71(6):1386-94
references.pmid: 12439824
references.citation: Am J Hum Genet. 2006 Apr;78(4):615-28
references.pmid: 16532392
references.citation: Nature. 2005 Oct 27;437(7063):1299-320
references.pmid: 16255080
references.citation: Proc Natl Acad Sci U S A. 2002 May 28;99(11):7335-9
references.pmid: 12032283
references.citation: Am J Hum Genet. 2005 Dec;77(6):988-98
references.pmid: 16380910
references.citation: Am J Hum Genet. 2007 Jan;80(1):112-25
references.pmid: 17160899
references.citation: Genet Epidemiol. 2006 Dec;30(8):703-17
references.pmid: 16986163
references.citation: Bioinformatics. 2005 May 1;21(9):2001-7
references.pmid: 15699029
references.citation: Hum Hered. 2002;54(4):186-98
references.pmid: 12771551
references.citation: Diabetes. 2004 Sep;53(9):2487-91
references.pmid: 15331565
references.citation: Genet Epidemiol. 2005 Dec;29(4):353-64
references.pmid: 16173096
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Nat Genet. 2001 Oct;29(2):229-32
references.pmid: 11586305
references.citation: Hum Mol Genet. 2000 Mar 22;9(5):725-33
references.pmid: 10749979
references.citation: Genetics. 1987 Oct;117(2):331-41
references.pmid: 3666445
references.citation: Am J Hum Genet. 2003 Sep;73(3):502-15
references.pmid: 12916017
references.citation: Bioinformatics. 2002 Feb;18(2):337-8
references.pmid: 11847089
references.citation: Hum Genet. 2005 Nov;118(2):276-86
references.pmid: 16184404