range of conditions and those directly simulating ascertainment variability across a wider range of conditions, the downward bias was as much as approximately 20% and approximately 50%, respectively (Table 1; Figure S1 in Supplement 1). Second, both the field standard and our proposed approaches produce the same estimates when ascertainment is equivalent across all cohorts (Figure 1B, L). Importantly, the standard procedure of using total sample prevalence (vTotal) is not biased as a function of the overall degree of ascertainment. Rather, the bias is attributable to the level of ascertainment variability across cohorts. Third, our proposed procedure of using ∑EffNk removes this bias, producing accurate estimates of the population-level, liability-scale heritability (Table 1 and Figure 1) across a range of population generating conditions (Table S1 in Supplement 2). Having established that using P EffNk produces an accurate estimate of hl2, we went on to examine the difference across using vTotal and ∑EffNk in real data.
