Sample sizes used for the initial identification of DNA sequence variants have generally been modest, and sample size requirements increase essentially linearly with 1/MAF. Much larger samples are needed for the identification of associations with variants than those needed for the detection of the variants themselves. They also scale roughly linearly with 1/MAF given a fixed odds ratio and fixed degree of linkage disequilibrium with genotyped markers. Sample size for association detection also scales approximately quadratically with 1/|(OR−1)|, and thus increases sharply as the odds ratio (OR) declines. Sample size is even more strongly affected by small odds ratios than by small MAF, so low frequency and rare variants will need to have higher odds ratios to be detected.
