A comparison between different designs and tests to detect QTLs in association studies

The availability of different designs and tests to detect QTLs in association studies raises questions about the relative merits of the various approaches. We therefore compared the power of quantitative versus categorical tests, the power in population samples versus samples with subjects selected on the basis of their trait scores, and the power of tests that control for population stratification using parental genotypes versus tests that do not control for stratification. In case-control samples the power of quantitative tests was clearly better than that of categorical tests especially when the control group was a population sample. In samples of genotyped trios of cases and their parents, the power of quantitative tests was much poorer. Compared to population samples, selection always improved the power in case-control samples where the controls were sampled from the opposite end of the continuum and frequently deteriorated the power when the controls were a population sample, Mainly because subjects with at least one heterozygous parent need to be selected, the use of tests that control for stratification resulted in a substantial decrease of power. In the final section our power calculations were integrated into a more general discussion about optimizing designs in association studies.