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

Nat Genet. 2005 Jul;37(7):683-91. doi: 10.1038/ng1582. Epub 2005 Jun 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Asthma / genetics
  • Computer Simulation
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Haplotypes
  • Humans
  • Interleukin-10 / genetics
  • Linkage Disequilibrium*
  • Pedigree*
  • Polymorphism, Single Nucleotide
  • Software

Substances

  • Interleukin-10