Power of Genetic Association Studies with Fixed and Random Genotype Frequencies

Julia Kozlitina, Chao Xing, Alexander Pertsemlidis, William R. Schucany

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


When estimating the power of genetic association studies, the allele and genotype frequencies are often assumed to be known, and the numbers of individuals with each genotype are set equal to their expectations under Hardy-Weinberg equilibrium. In fact, both allele and genotype frequencies are unknown and thus random. It has previously been suggested that ignoring uncertainty in these parameters could lead to inflated power expectations. To overcome the problem, one can average power estimates over the distributions of unknown frequencies. We investigate the power-averaging method and find that, despite the intuitive appeal, it may not improve accuracy in practice, while significantly increasing computational time. For a fixed allele frequency, we show that the amount of overestimation diminishes rapidly with sample size and is completely negligible for N > 200. For an unknown frequency, the result of averaging depends on the genetic model, and may not always provide a more conservative estimate of power. We explore the effect of uncertainty in the factors that determine statistical power of association studies and propose a more economical approach to the power analysis.

Original languageEnglish (US)
Pages (from-to)429-438
Number of pages10
JournalAnnals of Human Genetics
Issue number5
StatePublished - Sep 2010
Externally publishedYes


  • Allele frequency
  • Average power
  • Sample size
  • Sensitivity to model assumptions

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


Dive into the research topics of 'Power of Genetic Association Studies with Fixed and Random Genotype Frequencies'. Together they form a unique fingerprint.

Cite this