The reasons for discarding these SNPs may be related to genotyping issues, such as lower genotyping rates or concerns about calling accuracy. However, discarding low-MAF SNPs may also be due to perceptions about the statistical inferences that result from analyzing such SNPs. Anecdotally, investigators have expressed "distrust" of significant results arising from low-MAF SNPs. However, a recent study demonstrated that in the absence of bias in genotype error rates between cases and controls, even very small MAFs show type I error rates close to nominal levels [6]. Our study confirms and extends this report, showing that nominally significant results occur significantly less often than expected, even for low MAF SNPs, resulting in a conservative bias. Thus, our findings do not support the removal of low MAF SNPs from analysis due to concerns about inflated false-positive results.
