Case-Parents Design for Gene-Environment Interaction
Daniel J. Schaid
Genetic Epidemiology ,
16(3):261-273 (1999).
Abstract
The scientific and public health implications of gene-environment interaction
warrant that the most powerful study designs and methods of analysis be
used. Because traditional case-control designs, which use nonrelated
subjects, have demonstrated the need for large samples to detect interactions,
alternative study designs may be worthwhile, such as sampling diseased cases
and their parents. If the transmission of particular alleles from
parents to their diseased child appears to be distorted from
Mendelian expectation, then this suggests an etiologic association
of the alleles with disease; if the frequency
of transmission differs between exposed and nonexposed cases, then
gene-environment interaction is suggested. We present likelihood-based
methods to assess interaction, as well as an extension of the
transmission/disequilibrium test (TDT). For these statistical tests, we also
derive methods to compute sample size and power. Comparisons of sample
size requirements between the case-parents design and the case-control
design indicate that the case-parents design can be more powerful to detect
gene-environment interactions, particularly when the disease susceptible allele
is rare. Also, one of the derived likelihood methods, based on additive effects
of alleles, tended to be the most robust in terms of power for a broad range of
genetic mechanisms, and so may be useful for broad applications to assess
gene-environment interactions.
Association Studies