The impacts of errors in individual genotyping and DNA pooling on association studies

Case-control association studies using unrelated individuals may offer an effective approach for identifying genetic variants that have small to moderate disease risks. In general, two different strategies may be employed to establish associations between genotypes and phenotypes: (1) collecting individual genotypes or (2) quantifying allele frequencies in DNA pools. These two technologies have their respective advantages. Individual genotyping gathers more information, whereas DNA pooling may be more cost effective. Recent technological advances in DNA pooling have generated great interest in using DNA pooling in association studies. In this article, we investigate the impacts of errors in genotyping or measuring allele frequencies on the identification of genetic associations with these two strategies. We find that, with current technologies, compared to individual genotyping, a larger sample is generally required to achieve the same power using DNA pooling. We further consider the use of DNA pooling as a screening tool to identify candidate regions for follow-up studies. We find that the majority of the positive regions identified from DNA pooling results may represent false positives if measurement errors are not appropriately considered in the design of the study. Genet Epidemiol 26:1–10, 2004. & 2003 Wiley-Liss, Inc. Key words: case-control study; individual genotyping; DNA pooling; measurement error; sample size; false discover