Genomic screening and replication using the same data set in family-based association testing

K Van Steen, MB McQueen, A Herbert, B Raby… - Nature …, 2005 - nature.com
K Van Steen, MB McQueen, A Herbert, B Raby, H Lyon, DL DeMeo, A Murphy, J Su, S Datta…
Nature genetics, 2005nature.com
Abstract The Human Genome Project and its spin-offs are making it increasingly feasible to
determine the genetic basis of complex traits using genome-wide association studies. The
statistical challenge of analyzing such studies stems from the severe multiple-comparison
problem resulting from the analysis of thousands of SNPs. Our methodology for genome-
wide family-based association studies, using single SNPs or haplotypes, can identify
associations that achieve genome-wide significance. In relation to developing guidelines for …
Abstract
The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome-wide family-based association studies, using single SNPs or haplotypes, can identify associations that achieve genome-wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease-susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease-susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype-tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome-wide significance, as population-based designs do.
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