Observed heritability (h² obs) and its standard error (SE), expected heritability (h² exp) and the adjusted P-value from LD-score regression for enrichment in CAD.

<p>Also, the distances between p-value distributions (D-statistics) from Kolmogorov-Smirnov tests are shown, comparing different MAF groups: (a) [0.005–0.01) vs. [0.01–0.05); (b) [0.005–0.001) vs. (≥0.05); (c) [0.01–0.05) vs. (≥0.05).</p

Proportion of causal variants reaching significance as a function of the average effect and proportion of causal variants on average in a gene, employing a SNP-by-SNP analysis.

<p>Proportion of causal variants reaching significance as a function of the average effect and proportion of causal variants on average in a gene, employing a SNP-by-SNP analysis.</p

Dichotomous traits: Relationship between effect size, proportion of causal variants, and power, when causal variants only have a deleterious effect.

<p>Each box corresponds to a different proportion of causal variants involved in the relationship between rare variants and continuous traits (from left to right, 10, 15, 20 and 30%). On the x-axis, effect sizes are in standard deviations and correspond to the absolute value of the average size effect.</p

Number of SNPs by minor allele frequency bins, as well as the number and percentage of significant SNPs, using several definitions of statistical significance.

<p>Number of SNPs by minor allele frequency bins, as well as the number and percentage of significant SNPs, using several definitions of statistical significance.</p

Changes in LFDR estimates between unadjusted LFDR and LFDR estimated with the ME method, when each of nine functional annotations are used to define a high risk subset of SNPs.

<p>Within each panel, the three distributions are divided by p-value ranges: unadjusted p<0.05; unadjusted p<0.01; unadjusted p<0.001.</p

Power across all methods, per scenario, as described in <b>Table 1</b>, for the average across the seven genes.

<p>Footnote: Note that in some scenarios, different methods overlap. This is the case for scenario 1 and 2, where all methods give similar power.</p

LFDR estimates with the ME method, as a function of the –log(10) of the raw p-values, for all nine SNP annotation categories considered.

<p>LFDR estimates with the ME method, as a function of the –log(10) of the raw p-values, for all nine SNP annotation categories considered.</p

Scatter plot of the LFDR-ME estimates by minor allele frequency and the decrease in LFDR estimates using the ME method, when using the H3K9ac annotation.

<p>Scatter plot of the LFDR-ME estimates by minor allele frequency and the decrease in LFDR estimates using the ME method, when using the H3K9ac annotation.</p

Description of the count of rare variants per gene.

<p>Description of the count of rare variants per gene.</p

Summary of phenotype simulations and hypotheses.

<p>Summary of phenotype simulations and hypotheses.</p