Statistical power to detect gene-based associations in simulations.
Statistical power (proportion of simulation replicates in which gene-based p-value ≤2.5 × 10−6 across loci; y-axis) for each gene-based testing approach (x-axis & color) stratified by locus heritability (plot rows) when coding, eQTL, enhancer, UTR variants, or a mixture of these (“heterogeneous across loci”) are causal (plot columns). In the rightmost column, either coding, eQTL, enhancer, or UTR variants are causal with equal probability (as when the causal annotation class is heterogeneous across loci for a single trait). Power is shown separately for causal genes and proximal genes (non-causal genes that are proximal to a causal gene, as defined in Materials and methods). Ideally, gene-based tests should have high power for causal genes, and relatively lower power for proximal genes. Error bars show 95% confidence intervals for average power across loci.