Differences between our heritability estimates and those of previous studies can also be due to differences between the value of FSTC we used in this study and the true value of FSTC for the phenotype in question. Based on recent evidence that rare variants unlikely to contribute to a large proportion of phenotypic variation25,26, we computed an FSTC of 0.182 over the common variants (MAF > 5%) in African-Americans. However, this estimate drops to 0.165 for low-frequency variants (MAF < 5%) and 0.054 for rare variants (MAF < 1%). Estimates of heritability assuming a rare variant only phenotype model would be more than three times as large as from a common variant only phenotype model. Therefore, if rare variants contribute substantially to phenotypic variation or if balancing or negative selection constrained the genetic distance at causal variants, then our estimates of heritability will be biased downward (see Discussion).
