DATA-DREDGING GENE-DOSE ANALYSES IN ASSOCIATION STUDIES: BIASES AND THEIR CORRECTIONS

To examine the joint effect of multiple loci on disease risk , many case-control association studies used "gene-dose analyses." However, some researchers defined high-risk genotypes (or alleles) as those that have higher genotypic ( allelic) frequencies in the case group compared with the control group in the study. This will lead to the total number of the "high-risk" genotypes (alleles) tending to be higher for the cases than for the controls as well, even if none of the studied loci were related to the disease. Monte- Carlo simulations done in this study showed that such a " data-dredging" gene-dose analysis could produce grossly biased results. A permutation correction method was proposed which could correct the biases very effectively.