It has been shown that pLI is correlated with gene expression across tissues, including brain21, which raises the possibility that the enrichment for LoF-intolerant genes in schizophrenia may reflect enrichment for signal in genes expressed in the brain. However, LoF-intolerant gene set enrichment was robust to the inclusion of both ‘brain-expressed’ (n = 10,360) and ‘brain-specific’ (n = 2,647) gene sets19 as covariates in the analysis (P = 1.89 × 10−10) or to controlling for FPKM gene expression values in brain22 (P = 1.03 × 10−14).
