Genomic screening and replication using the same data set in family-based association testing.
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.
Van Steen
Kristel
K
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. kvanstee@hsph.harvard.edu
McQueen
Matthew B
MB
Herbert
Alan
A
Raby
Benjamin
B
Lyon
Helen
H
Demeo
Dawn L
DL
Murphy
Amy
A
Su
Jessica
J
Datta
Soma
S
Rosenow
Carsten
C
Christman
Michael
M
Silverman
Edwin K
EK
Laird
Nan M
NM
Weiss
Scott T
ST
Lange
Christoph
C
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
D016753:Interleukin-10