I. Foppa et D. Spiegelman, POWER AND SAMPLE-SIZE CALCULATIONS FOR CASE-CONTROL STUDIES OF GENE-ENVIRONMENT INTERACTIONS WITH A POLYTOMOUS EXPOSURE VARIABLE, American journal of epidemiology, 146(7), 1997, pp. 596-604
Genetic polymorphisms may appear to the epidemiologist most commonly a
s different levels of susceptibility to exposure. Epidemiologic studie
s of heterogeneity in exposure susceptibility aim at estimating the pa
rameter quantifying the gene-environment interaction, In this paper, t
he authors use a general approach to power and sample size calculation
s for case-control studies, which is applicable to settings where the
exposure variable is polytomous and where the assumption of independen
ce between the distribution of the genotype and the environmental fact
or may not be met. It was found through exploration of different scena
rios that in the cases explored, power calculations were relatively in
sensitive to assumptions about the odds ratio for the exposure in the
referent genotype category and to assumptions about the odds ratio for
the genetic factor in the lowest exposure category, yet they were rel
atively sensitive to assumptions about gene frequency, particularly wh
en gene frequency was low. In general, to detect a small to moderate g
ene-environment interaction effect, large sample sizes are needed. Bec
ause the examples studied represent only a small subset of possible sc
enarios that could occur in practice, the authors encourage the use of
their user-friendly Fortran program for calculating power and sample
size for gene-environment interactions with exposures grouped by quant
iles that are explicitly tailored to the study at hand.