Positive selection acting at causal variants could induce such a bias in FSTC, and we included WBC as a positive control for this type of bias. A SNP in the DARC gene (FY, Duffy null allele) is highly differentiated between CEU and YRI, likely due to its protective effect against vivax malaria27. It is also a SNP of large effect size for WBC28. Therefore, the average FSTC at causal variants for WBC, is much higher than the value 0.182 estimated from common variants (see Online Methods). The h2 estimate of WBC is 3.42 due to the effect of this positive selective pressure. Ancestry at the FY locus accounts for ∼20% of the phenotypic variation in WBC28. By including ancestry at FY as a fixed effect (WBC|FY) we obtain an h2 estimate of 0.19, which is lower than the published estimate of 0.48.
