Power analysis for case-control association studies of samples with known family histories

Hum Genet. 2010 Jun;127(6):699-704. doi: 10.1007/s00439-010-0824-5. Epub 2010 Apr 11.


Genome-wide case-control studies have been widely used to identify genetic variants that predispose to human diseases. Such studies are powerful in detecting common genetic variants with moderate effects, but quickly lose power as allele frequency and genotype relative risk decrease. Because patients with one or more affected relatives are more likely to inherit disease-predisposing alleles of a genetic disease than patients without family histories of the disease, sampling patients with affected relatives almost always increases the frequency of disease predisposing alleles in cases and improves the power of case-control association studies. This paper evaluates the power of case-control studies that select cases and/or controls according to their family histories of disease. Our results showed that this study design can dramatically increase the power of a case-control association study for a wide range of disease types. Because each additional affected relative of a patient reduces the required sample size roughly by a pair of case and control, inclusion of cases with affected relatives can dramatically decrease the required sample size and thus the cost of such studies.

Publication types

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

MeSH terms

  • Alleles
  • Case-Control Studies*
  • Gene Frequency
  • Genetic Diseases, Inborn / genetics*
  • Genotype
  • Humans
  • Research Design*
  • Research*
  • Risk
  • Sample Size*