To quantify the contribution of SNPs within LoF-intolerant genes to schizophrenia SNP-based heritability (h2SNP), we used partitioned linkage disequilibrium score regression (LDSR)26 (Supplementary Table 7). Overall, genic SNPs accounted for 64% of h2SNP, a 1.23-fold enrichment proportional to their SNP content (P = 5.93 × 10−14). Consistent with the analysis using MAGMA, h2SNP was enriched in LoF-intolerant genes (2.01-fold; P = 2.78 × 10−24), which explained 30% of all h2SNP (equating to 47% of all genic h2SNP). In contrast, genes classed as not LoF intolerant (pLI < 0.9) were significantly depleted for h2SNP relative to their SnP content (0.90-fold; P = 5.86 × 10−3), although in absolute terms SNPs in these genes accounted for 34% of h2SNP A finer-scale analysis of the relationship between LoF intolerance scores and enrichment for association showed that enrichment was restricted to genes with a pLI score above 0.9, precisely those defined as ‘LoF intolerant’ (Supplementary Fig. 5).
