As shown in the equations above we are defining FST to be the weighted average (across all SNPs s) of ratios (ps,1−ps,0)2σg,s2. While this is similar to standard versions of FST, a ratio of averages is recommended instead when the goal is to draw population genetic inferences47. If the distribution of SNPs effect sizes is not a function FST then this would be the appropriate definition for our heritability estimation approach. However, recent work has shown that rare variants are unlikely to contribute to a large proportion of phenotypic variation48,25. As has been reported previously47, the average of ratios estimate will shrink when including many rare variants in the estimate. This is reflected in the 1000 Genomes based estimate of FST =0.07, which used an average of ratios49. Therefore, FST will produce a biased estimate of heritability because for the variance explained by rare variants is different from the variance explained by common variants. To account for this we defined a parameter FSTC, which is a weighted measure of genetic distance between ancestral populations (equation 9).
