However, our study does raise the concern about ranking p-values generated from SNPs across vastly different MAF. Given our findings, we suggest that the χ2 threshold to establish a particular level of significance may need to be modified using empirical permutations for several MAF "bins." For example, in our analysis dataset, for an MAF of 25% and a significance threshold of 10-5, the threshold χ2 value would need to be reduced from 19.51 (from the standard χ2 distribution) to 18.79 to capture the expected 10 false positives. However, it should be noted that to determine robust estimates, χ2 adjustments, and false positive rates for a GWAS significance of 10-8, over 10 billion permutations and significant computing capability would be required. Additional studies using larger datasets will be required to fully understand this issue.
