Comparison of type 1 error rate simulation results across models.

Shown is the type 1 error rate (at significance threshold of 0.05) of the five different TWAS models and LAVA-rG for the null hypothesis of no genetic covariance (cov(GE, GY) = 0), at different levels of local heritability (h2) for outcome phenotype (horizontal axis) and gene expression (separate panels). Results are shown for sample sizes of 1,000 and 100,000 for the expression and outcome respectively, with 1,000 SNPs. As shown, the results are very similar across the different models. The lower type 1 error rate for Elastic Net and LASSO compared to the other TWAS models for the 1% expression heritability condition is due to these two models sometimes failing to converge at very low genetic signal for the expression (see also Fig D in S1 Text).