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Detecting local haplotype sharing and haplotype association.

dc.contributor.author Guan, Yongtao
dc.contributor.author Xu, Hanli
dc.date.accessioned 2018-07-25T18:02:34Z
dc.date.available 2018-07-25T18:02:34Z
dc.date.issued 2014-07
dc.identifier.issn 0016-6731
dc.identifier.issn 1943-2631
dc.identifier.uri https://hdl.handle.net/10161/17275
dc.description.abstract A novel haplotype association method is presented, and its power is demonstrated. Relying on a statistical model for linkage disequilibrium (LD), the method first infers ancestral haplotypes and their loadings at each marker for each individual. The loadings are then used to quantify local haplotype sharing between individuals at each marker. A statistical model was developed to link the local haplotype sharing and phenotypes to test for association. We devised a novel method to fit the LD model, reducing the complexity from putatively quadratic to linear (in the number of ancestral haplotypes). Therefore, the LD model can be fitted to all study samples simultaneously, and, consequently, our method is applicable to big data sets. Compared to existing haplotype association methods, our method integrated out phase uncertainty, avoided arbitrariness in specifying haplotypes, and had the same number of tests as the single-SNP analysis. We applied our method to data from the Wellcome Trust Case Control Consortium and discovered eight novel associations between seven gene regions and five disease phenotypes. Among these, GRIK4, which encodes a protein that belongs to the glutamate-gated ionic channel family, is strongly associated with both coronary artery disease and rheumatoid arthritis. A software package implementing methods described in this article is freely available at http://www.haplotype.org.
dc.language eng
dc.relation.ispartof Genetics
dc.relation.isversionof 10.1534/genetics.114.164814
dc.subject Humans
dc.subject Genetic Predisposition to Disease
dc.subject Bayes Theorem
dc.subject Case-Control Studies
dc.subject Haplotypes
dc.subject Linkage Disequilibrium
dc.subject Phenotype
dc.subject Polymorphism, Single Nucleotide
dc.subject Alleles
dc.subject Algorithms
dc.subject Models, Genetic
dc.subject Computer Simulation
dc.subject Databases, Genetic
dc.subject Genetic Association Studies
dc.title Detecting local haplotype sharing and haplotype association.
dc.type Journal article
dc.date.updated 2018-07-25T18:02:28Z
pubs.begin-page 823
pubs.end-page 838
pubs.issue 3
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Basic Science Departments
pubs.publication-status Published
pubs.volume 197
duke.contributor.orcid Guan, Yongtao|0000-0002-8055-2192


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