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Chunk #39 — Methods — Two-Step Estimator

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An atlas of genetic correlations across human diseases and traits.
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then we can make the task much easier by removing those SNPs. However, this is unsatisfactory if the goal is to estimate h2: ignoring large-effect SNPs with χ2>80 would bias estimates of h2 and ρg towards zero. Therefore, for estimating h2 or ρg, we take a two step approach. The first step is to estimate the LD Score regression intercept with all SNPs with χ2>30 removed (i.e., all genome-wide significant SNPs; the threshold can be adjusted with the -two-step flag in ldsc). The second step is to estimate h2 or ρg using all SNPs and constrained intercept LD Score regression with the intercept constrained to the value from the first step (note that we account for uncertainty in the intercept when computing a standard error; see the next section).