Scatter plots comparing how the integrative neural network training procedure enables the ability to identify associated SNPs and enriched SNP-sets in simulations (British cohort).

Quantitative traits are simulated to have broad-sense heritability of H2 = 0.6 with equal contributions from additive effects and epistatic interactions (i.e., ρ = 0.5). We consider two different trait architectures: (A, B) sparse where only 1% of SNP-sets are enriched for the trait; and (C, D) polygenic where 10% of SNP-sets are enriched. We set the number of causal SNPs with non-zero effects to be 1% and 10% of all SNPs located within the enriched SNP-sets, respectively. Results are shown comparing the posterior inclusion probabilities (PIPs) derived by the BANNs model fit with individual-level data on the x-axis and (A, C) SuSiE [46] and (B, D) RSS [26] on the y-axis, respectively. Here, SuSie is fit while assuming a high maximum number of causal SNPs (ℓ = 3000). The blue horizontal and vertical dashed lines are marked at the “median probability criterion” (i.e., PIPs for SNPs and SNP-sets greater than 0.5) [57]. True positive causal variants used to generate the synthetic phenotypes are colored in red, while non-causal variants are given in grey. SNPs and SNP-sets in the top right quadrant are selected by both approaches; while, elements in the bottom right and top left quadrants are uniquely identified by BANNs and SuSie/RSS, respectively. Each plot combines results from 100 simulated replicates (see S1 Text). (PDF)