Sample size requirements for matched case-control studies of gene-environment interaction

Stat Med. 2002 Jan 15;21(1):35-50. doi: 10.1002/sim.973.


Consideration of gene-environment (GxE) interaction is becoming increasingly important in the design of new epidemiologic studies. We present a method for computing required sample size or power to detect GxE interaction in the context of three specific designs: the standard matched case-control; the case-sibling, and the case-parent designs. The method is based on computation of the expected value of the likelihood ratio test statistic, assuming that the data will be analysed using conditional logistic regression. Comparisons of required sample sizes indicate that the family-based designs (case-sibling and case-parent) generally require fewer matched sets than the case-control design to achieve the same power for detecting a GxE interaction. The case-sibling design is most efficient when studying a dominant gene, while the case-parent design is preferred for a recessive gene. Methods are also presented for computing sample size when matched sets are obtained from a stratified population, for example, when the population consists of multiple ethnic groups. A software program that implements the method is freely available, and may be downloaded from the website

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Air Pollution / adverse effects
  • Asian
  • Asthma / etiology
  • BRCA1 Protein / adverse effects
  • BRCA1 Protein / genetics
  • Black or African American
  • Breast Neoplasms / etiology
  • California
  • Case-Control Studies*
  • Child
  • Contraceptives, Oral, Hormonal / adverse effects
  • Environmental Exposure / adverse effects*
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Glutathione Transferase / adverse effects
  • Glutathione Transferase / genetics
  • Hispanic or Latino
  • Humans
  • Models, Biological*
  • Models, Statistical*
  • Sample Size
  • White People


  • BRCA1 Protein
  • Contraceptives, Oral, Hormonal
  • Glutathione Transferase
  • glutathione S-transferase M1