It is known that the power of a gene set analysis is closely related to the total heritability of the phenotype and the specific heritability attributable to the tested gene set82. To assess the heritability explained by the genes carried forward after the main gene set analysis, LD Score was again used to compute a partitioned heritability estimate of CLOZUK + PGC using the gene sets as SNP annotations. As in the MAGMA analysis, the xMHC region was excluded from the summary statistics. These were also trimmed to contain no indels and only markers with INFO >0.9 and MAF >0.01, for a total of 4.64 million SNPs. As a recognized caveat of this procedure is that model misspecification can inflate the partitioned heritability estimates26, all gene sets were annotated twice: once using their exact genomic coordinates (extracted from the NCBI RefSeq database83) and another time with putative regulatory regions taken into account using the same upstream/downstream windows as in the MAGMA analyses. Additionally, all SNPs not directly covered by our gene sets of interest were explicitly included into other annotations
