Reference : A unified test of linkage analysis and rare-variant association for analysis of pedig...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.
Hu, Hao [> >]
Roach, Jared C. [> >]
Coon, Hilary [> >]
Guthery, Stephen L. [> >]
Voelkerding, Karl V. [> >]
Margraf, Rebecca L. [> >]
Durtschi, Jacob D. [> >]
Tavtigian, Sean V. [> >]
Shankaracharya [> >]
Wu, Wilfred [> >]
Scheet, Paul [> >]
Wang, Shuoguo [> >]
Xing, Jinchuan [> >]
Glusman, Gustavo [> >]
Hubley, Robert [> >]
Li, Hong [> >]
Garg, Vidu [> >]
Moore, Barry [> >]
Hood, Leroy [> >]
Galas, David J. [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Srivastava, Deepak [> >]
Reese, Martin G. [> >]
Jorde, Lynn B. [> >]
Yandell, Mark [> >]
Huff, Chad D. [> >]
Nature Biotechnology
Nature Publishing Group
Yes (verified by ORBilu)
New York
[en] Base Sequence ; Chromosome Mapping/methods ; DNA/genetics ; DNA Mutational Analysis/methods ; Genetic Linkage/genetics ; Genetic Markers/genetics ; Genetic Variation/genetics ; High-Throughput Nucleotide Sequencing/methods ; Molecular Sequence Data ; Pedigree
[en] High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)

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