Counter-matching in studies of gene-environment interaction: Efficiency and feasibility

The interest in studying gene-environment interaction is increasing for com plex diseases. However, most methods of detecting gene-environment interact ions may not be appropriate for the study of interactions involving rare ge nes (G) or uncommon environmental exposures (E), because of poor statistica l power. To increase this power, the authors propose the counter-matching d esign. This design increases the number of subjects with the rare factor wi thout increasing the number of measurements that must be performed. In this paper, the efficiency and feasibility (required sample sizes) of counter-m atching designs are evaluated and discussed. Counter-matching on both G and E appears to be the most efficient design for detecting gene-environment i nteraction. The sensitivity and specificity of the surrogate measures, the frequencies of G and E, and, to a lesser extent, the value of the interacti on effect are the most important parameters for determining efficiency. Fea sibility is also more dependent on the exposure frequencies and the interac tion effect than on the main effects of G and E. Although the efficiency of counter-matching is greatest when the risk factors are very rare, the stud y of such rare factors is not realistic unless one is interested in very st rong interaction effects. Nevertheless, counter-matching appears to be more appropriate than most traditional epidemiologic methods for the study of i nteractions involving rare factors.