Gene-Dose Analysis in Genetic Association Studies：A Potential Bias and its Correction

Many case-control association studies performed the “gene-dose analysis” to investigate the association between multiple loci and the disease. The authors found that the researchers in about one-third of these studies defined the high-risk genotypes (high-risk alleles) as those that have higher genotype frequencies (allele frequencies) in the case group than in the control in the study. The authors performed Monte-Carlo simulation and found that even though there is no association between each locus and the disease, this kind of definition will show false-positive gene-dose relationships. The authors proposed a permutation correction method which is easy to perform and can correct the biases very effectively. The permutation correction method may become a standard procedure for a valid gene-dose analysis in the days to come.