articleGenetic EpidemiologyFeb 25, 2008BRONZE OA

Estimation of significance thresholds for genomewide association scans

FDFrank DudbridgeAGArief Gusnanto

MRC Biostatistics Unit

PubMed
Indexed incrossrefpubmed

Abstract

The question of what significance threshold is appropriate for genomewide association studies is somewhat unresolved. Previous theoretical suggestions have yet to be validated in practice, whereas permutation testing does not resolve a discrepancy between the genomewide multiplicity of the experiment and the subset of markers actually tested. We used genotypes from the Wellcome Trust Case-Control Consortium to estimate a genomewide significance threshold for the UK Caucasian population. We subsampled the genotypes at increasing densities, using permutation to estimate the nominal P-value for 5% family-wise error. By extrapolating to infinite density, we estimated the genomewide significance threshold to be…

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Topics
Keywords
  • Estimator
  • Permutation (music)
  • Statistics
  • Multiple comparisons problem
  • Population
  • Resampling
  • Extrapolation
  • Mathematics
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