title: Genomic screening and replication using the same data set in family-based association testing.
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.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. kvanstee@hsph.harvard.edu
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Steen
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.forename: Alan
authors.initials: A
authors.lastname: Herbert
authors.forename: Benjamin
authors.initials: B
authors.lastname: Raby
authors.forename: Helen
authors.initials: H
authors.lastname: Lyon
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Demeo
authors.forename: Amy
authors.initials: A
authors.lastname: Murphy
authors.forename: Jessica
authors.initials: J
authors.lastname: Su
authors.forename: Soma
authors.initials: S
authors.lastname: Datta
authors.forename: Carsten
authors.initials: C
authors.lastname: Rosenow
authors.forename: Michael
authors.initials: M
authors.lastname: Christman
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D001249:Asthma / Q000235:genetics; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015810:Linkage Disequilibrium; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012984:Software
chemical_list: D016753:Interleukin-10