This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Halldórsson, B. V. Articles by Istrail, S. Search for Related Content PubMed PubMed Citation Articles by Halldórsson, B. V. Articles by Istrail, S. Social Bookmarking                   What's this?

Methods

Optimal Haplotype Block-Free Selection of Tagging SNPs for Genome-Wide Association Studies

¹ Celera/Applied Biosystems, Rockville, Maryland 20850, USA ² Applied Biosystems, Foster City, California 94404, USA ³ Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA

It is widely hoped that the study of sequence variation in the human genome will provide a means of elucidating the genetic component of complex diseases and variable drug responses. A major stumbling block to the successful design and execution of genome-wide disease association studies using single-nucleotide polymorphisms (SNPs) and linkage disequilibrium is the enormous number of SNPs in the human genome. This results in unacceptably high costs for exhaustive genotyping and presents a challenging problem of statistical inference. Here, we present a new method for optimally selecting minimum informative subsets of SNPs, also known as "tagging" SNPs, that is efficient for genome-wide selection. We contrast this method to published methods including haplotype block tagging, that is, grouping SNPs into segments of low haplotype diversity and typing a subset of the SNPs that can discriminate all common haplotypes within the blocks. Because our method does not rely on a predefined haplotype block structure and makes use of the weaker correlations that occur across neighboring blocks, it can be effectively applied across chromosomal regions with both high and low local linkage disequilibrium. We show that the number of tagging SNPs selected is substantially smaller than previously reported using block-based approaches and that selecting tagging SNPs optimally can result in a two- to threefold savings over selecting random SNPs.

⁴ Present address: University of California, San Diego, Computer Science & Engineering, La Jolla, CA 92093, USA

⁵ Present address: Department of Mathematics, MIT, Cambridge, MA 02139-4307, USA

⁶ Present address: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA

⁷ Corresponding author.
E-MAIL Sorin.Istrail{at}celera.com; FAX (240) 453-3324.

[Supplemental material is available online at www.genome.org.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Paschou, M. W. Mahoney, A. Javed, J. R. Kidd, A. J. Pakstis, S. Gu, K. K. Kidd, and P. Drineas Intra- and interpopulation genotype reconstruction from tagging SNPs Genome Res., January 1, 2007; 17(1): 96 - 107. [Abstract] [Full Text] [PDF]

				J. Zhao, L. Jin, and M. Xiong Nonlinear Tests for Genomewide Association Studies Genetics, November 1, 2006; 174(3): 1529 - 1538. [Abstract] [Full Text] [PDF]

				K. Bhasi, L. Zhang, D. Brazeau, A. Zhang, and M. Ramanathan VizStruct for visualization of genome-wide SNP analyses Bioinformatics, July 1, 2006; 22(13): 1569 - 1576. [Abstract] [Full Text] [PDF]

				R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]

				Z. S. Qin, S. Gopalakrishnan, and G. R. Abecasis An efficient comprehensive search algorithm for tagSNP selection using linkage disequilibrium criteria Bioinformatics, January 15, 2006; 22(2): 220 - 225. [Abstract] [Full Text] [PDF]

				X. Ke, M. M. Miretti, J. Broxholme, S. Hunt, S. Beck, D. R. Bentley, P. Deloukas, and L. R. Cardon A comparison of tagging methods and their tagging space Hum. Mol. Genet., September 15, 2005; 14(18): 2757 - 2767. [Abstract] [Full Text] [PDF]

				F. M. De La Vega, H. Isaac, A. Collins, C. R. Scafe, B. V. Halldorsson, X. Su, R. A. Lippert, Y. Wang, M. Laig-Webster, R. T. Koehler, et al. The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern Genome Res., April 1, 2005; 15(4): 454 - 462. [Abstract] [Full Text] [PDF]