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- Title
Genomic screening and replication using the same data set in family-based association testing.
- Authors
Van Steen, Kristel; McQueen, Matthew B.; Herbert, Alan; Raby, Benjamin; Lyon, Helen; DeMeo, Dawn L.; Murphy, Amy; Su, Jessica; Datta, Soma; Rosenow, Carsten; Christman, Michael; Silverman, Edwin K.; Laird, Nan M.; Weiss, Scott T.; Lange, Christoph
- 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.
- Subjects
GENOMES; HUMAN gene mapping; CORPORATE reorganizations; DISEASE susceptibility; ETIOLOGY of diseases; DIAGNOSIS
- Publication
Nature Genetics, 2005, Vol 37, Issue 7, p683
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng1582