All genes were divided into 10 bins based on the average expression value of the TMM-normalized and log2-transformed expression matrix from BIOS cohort. If the number of tested genes did not divide by 10, the lowest bin was set to include more genes than the rest of the bins. ExAC pLI metrics19 were acquired from ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cleaned_exac_r03_march16_z_pli_rec_null_data.txt. For every expression bin, genes for which pLI metric was available were tested for difference by two-sided Wilcoxon rank sum test.
