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Chunk #7 — METHODS AND MATERIALS — Simulating Ascertainment Variability

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Pervasive Downward Bias in Estimates of Liability-Scale Heritability in Genome-wide Association Study Meta-analysis: A Simple Solution.
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We went on then to perform a series of simulations that relied on this property by generating a wide variety of cohort-specific sample sizes and analytically computing bias in the heritability estimate, rather than generating GWAS summary statistics and estimating heritability. We began by performing a set of simulations that mirrored the simulating conditions when GWAS summary statistics were generated (i.e., mixtures of cohorts consisting of 50%/50% and 10%/90% cases/control ratios) to confirm the equivalence of the 2 approaches. We then expanded the range of simulating conditions to consider the full scope of potential bias within a plausible range. This involved running 1000 simulations that all consisted of generating 10 cohorts of 1000 participants, with each cohort set to randomly contain a proportion of cases between 5% and 95%.