by a lower limit threshold. SNPs with frequency too low to yield reasonable statistical power (e.g. below 1%) may be removed from the analysis to lighten the computational and multiple testing correction burden. However, in studies with very large sample sizes it may be beneficial to avoid removing these rare SNPs. Others have shown that nonsynonymous, possibly deleterious SNPs are on average rarer than synonymous SNPs that likely do not cause any adverse phenotypes [45].