Nature Genetics 38, 663 - 667 (2006)
Published online: 21 May 2006; | doi:10.1038/ng1816
Evaluating and improving power in whole-genome association studies using fixed marker setsItsik Pe'er1, 4, 5, Paul I W de Bakker1, 2, 4, 6, Julian Maller1, Roman Yelensky1, 2, 7, David Altshuler1, 2, 3, 4, 5, 6
& Mark J Daly1, 4, 51
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. 2
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. 3
Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. 4
Broad Institute of M.I.T. and Harvard, Cambridge, Massachusetts 02142, USA. 5
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. 6
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. 7
Harvard-M.I.T. Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA.
Correspondence should be addressed to Mark J Daly mjdaly@chgr.mgh.harvard.edu or David Altshuler altshul@broad.mit.edu Emerging technologies make it possible for the first time to genotype hundreds of thousands of SNPs simultaneously, enabling whole-genome association studies. Using empirical genotype data from the International HapMap Project, we evaluate the extent to which the sets of SNPs contained on three whole-genome genotyping arrays capture common SNPs across the genome, and we find that the majority of common SNPs are well captured by these products either directly or through linkage disequilibrium. We explore analytical strategies that use HapMap data to improve power of association studies conducted with these fixed sets of markers and show that limited inclusion of specific haplotype tests in association analysis can increase the fraction of common variants captured by 25–100%. Finally, we introduce a Bayesian approach to association analysis by weighting the likelihood of each statistical test to reflect the number of putative causal alleles to which it is correlated.
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