Fig. 3: The transcriptome-wide significant gene-disease association signals of NR5A2 (1q32.1), SATB2 (2q33.1), and PPP3CA (4q24) for SCZ, CD, and UC largely explain fine-mapped GWAS association signals from nearby GWAS susceptibility loci.

a The gene-disease association signal of NR5A2 is driven by the nearby but nonoverlapping established SCZ and CD/UC GWAS signals located 104 and 654 kilobases (kb) upstream of NR5A2, respectively (Table 2). Increased genetically regulated expression of NR5A2 in the hypothalamus and colon transversum was associated with increased risk for schizophrenia (SCZ), Crohn’s disease (CD), and ulcerative colitis (UC). b The association signal of SATB2 is driven by the nearby but nonoverlapping established SCZ and UC GWAS signals located 67 and 424 kilobases (kb) downstream and upstream of SATB2, respectively. Increased genetically regulated expression of SATB2 in frontal cortex BA9 and colon sigmoideum is associated with increased risk for SCZ and UC. Although 95% credible sets of variants most likely to be causal (red circles; upper part) differ between SCZ and UC, the distribution pattern of TWAS gene eQTLs of SATB2 (gray asterisks [upper part] and green transparent circles [middle part]) leads to the shared gene-disease association for SATB2 in both SCZ and UC. c The gene-disease association signal of PPP3CA is driven by the nearby (nonoverlapping) established SCZ and CD GWAS signals located 280 and 383 kilobases (kb) upstream of SATB2, respectively. Decreased genetically regulated expression of PPP3CA in putamen basal ganglia and colon transversum is associated with increased risk for SCZ and CD. Raw data of this figure can be found in Supplementary Data 16. Explanation of figure elements: Subplots include original consortium GWAS SNP summary statistics of size ±1 Mb (gray circles; upper part) around the gene, with the 95% credible sets of variants most likely to be causal at each locus (red circles; upper part) as defined by GWAS fine-mapping studies^31,33. SNP summary stats were conditioned (black circles; upper part) on TWAS gene eQTLs (black asterisks [upper part] correspond to the green transparent circles [middle part], with the relative absolute weight of the eQTLs visualized by the size of green transparent circles) to examine if the original GWAS SNP statistics (gray circles [upper part]; gray asterisks correspond to the green transparent circles [middle part]) can be explained by genetically regulated expression of the gene (green rectangles depict unconditioned/conditioned TWAS P values from Single-tissue_conditional analysis; lower part). GWAS SNP summary statistics of 95% credible sets of variants after joint GWAS/TWAS fine-mapping analysis are depicted as light green circles (upper part). Gene-start and gene end positions are marked by dumbbell-shaped black bars (middle part).