8 CHAPTER 8 174 than expected based on the overall number of cis-eQTLs per tissue reported by GTEx (Supplementary Figure 4 and Supplementary Note). To prioritize candidate genes for the risk loci, we applied two approaches based on GTEx v8 expression data: fine-mapping of causal gene-sets by FOCUS67 (Supplementary Table 11A) and a transcriptome-wide association study (TWAS) by S-PrediXcan65 combined with colocalization analysis using COLOC66 (Supplementary Table 11B). With posterior probability (PP) > 0.5, FOCUS found candidate genes for 82 loci and S-PrediXcan + COLOC supported colocalization for 52 loci (Supplementary Table 11C). In total, 73 genes in 46 loci were prioritized by both methods. MRC2 and PHACTR1 were the only genes that both methods prioritized with strong evidence (PP > 0.99 for same tissue) and without any other gene prioritized within their loci. Table 3 LDSC-SEG results that are significant at FDR 5% Tissue/cell type and histone mark Tissue category P-value FDR adjusted P-value Multi-tissue gene expression data Aorta Cardiovascular 1.78E-04 0.029 Tibial artery Cardiovascular 3.60E-04 0.029 Coronary artery Cardiovascular 4.29E-04 0.029 Gene expression data of 13 brain regions from GTEx Caudate (basal ganglia) Central nervous system 6.00E-04 0.008 Multi-tissue chromatin annotation data Fetal brain female, H3K4me3 Central nervous system 2.49E-05 0.012 Brain dorsolateral prefrontal cortex, H3K27ac Central nervous system 8.43E-05 0.018 Brain dorsolateral prefrontal cortex, H3K4me3 Central nervous system 1.11E-04 0.018 Aorta, H3K4me1 Cardiovascular 2.57E-04 0.031 Stomach mucosa, H3K36me3 Digestive 3.36E-04 0.032 Aorta, H3K27ac Cardiovascular 4.40E-04 0.032 Artery-tibial ENTEX, H3K4me1 Cardiovascular 4.53E-04 0.032 Ganglion eminence derived primary cultured neurospheres, H3K4me3 Central nervous system 6.53E-04 0.04 Brain germinal matrix, H3K4me3 Central nervous system 8.42E-04 0.043 Aorta ENTEX, H3K27ac Cardiovascular 1.11E-03 0.043 Artery-coronary ENTEX, H3K4me3 Cardiovascular 1.13E-03 0.043 Cortex derived primary cultured neurospheres, H3K36me3 Central nervous system 1.14E-03 0.043 Ovary, H3K27ac Other 1.15E-03 0.043 Cortex derived primary cultured neurospheres, H3K4me3 Central nervous system 1.29E-03 0.045 Aorta ENTEX, H3K4me1 Cardiovascular 1.39E-03 0.045 Stomach smooth muscle, H3K4me3 Musculoskeletal/connective 1.55E-03 0.047 One-sided P-value from testing whether the regression coefficient is positive. FDR, false discovery rate based on Benjamini-Hochberg method. Full results are in Supplementary Table 14A-F.
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