Potential for Gene–Gene Confounding Bias in Case–Parental Control Studies

PURPOSE: To show the potential for gene–gene confounding bias in case–parental control studies. METHODS: The authors quantify the magnitude of gene–gene confounding bias using simple mathematical equations. They also demonstrate the potential problems of such a bias with hypothetical (but realistic) examples. RESULTS: The degree of bias resulting from gene–gene confounding was found to be quite substantial under certain conditions (two genes are very closely linked and/or the study was performed in a recently admixed population). CONCLUSION: In this post–genomic era more and more encounters of the gene–gene confounding will be expected, if the one-gene-at-a-time approach continues to be adopted.