We conducted bioannotation and bioinformatic analyses to further characterize the loci identified by the TUD GWAS (Supplementary Methods). We used the default version (v1.3.6a) of the FUMA web-based platform41 to identify independent SNPs (r2<0.10) and to study their functional consequences. We also used MAGMA v1.0841,42 to perform competitive gene-set and pathway analyses. SNPs were mapped to 19,532 protein-coding genes from Ensembl (build 85). We applied a Bonferroni correction based on the total number of genes tested (p<2.63E−06). Gene sets were obtained from Msigdb v7.0 (“Curated gene sets”, “GO terms”). We also used Hi-C coupled MAGMA (H-MAGMA43) to assign non-coding (intergenic and intronic) SNPs to genes based on their chromatin interactions. Exonic and promoter SNPs were assigned to genes based on physical position. H-MAGMA uses four Hi-C datasets, which were derived from fetal brain, adult brain, iPSC-derived neurons, and iPSC-derived astrocytes (https://github.com/thewonlab/H-MAGMA). We applied a Bonferroni correction based on the total number of gene-tissue pairs tested (p<9.44E−07).
