. 2022 Jan 20;5:80. doi: 10.1038/s42003-022-03031-6

Table 2.

Transcriptome-wide significant susceptibility genes (NR5A2, SATB2, PPP3CA) shared between schizophrenia and inflammatory bowel diseases expressed in the gut-brain axis (GBA) tissues.

Gene	Gene-start-end (in kb)	(h_med-min², h_med-max²) in %	Primary tissue(s) of strongest gene-disease association	Diseases primary tissue(s)	Secondary tissue(s) of gene-disease association	Z_marginal primary tissue			P_conditional primary tissue			Overlap with GWAS locus	Distance to GWAS locus
Gene	Gene-start-end (in kb)	(h_med-min², h_med-max²) in %	Primary tissue(s) of strongest gene-disease association	Diseases primary tissue(s)	Secondary tissue(s) of gene-disease association	SCZ	CD	UC	SCZ	CD	UC	Overlap with GWAS locus	Distance to GWAS locus
NR5A2	chr1:199,996 - 200,146	(13.4, 18.2)	Hypothalamus	SCZ, CD, UC	SCZ:-; CD/UC: Colon transversum	4.86	5.82	7.7	1.63 × 10⁻⁶	3.66 × 10⁻⁸	1.97 × 10⁻¹³	No overlap	SCZ:104 kb; CD/UC:654 kb
SATB2	chr2:200,134 - 200,320	(6.9, 24.8)	Frontal Cortex BA9	SCZ, UC	SCZ: -; UC: Colon sigmoideum	4.75	-0.55	8.46	1.29 × 10⁻⁶	0.908	2.27 × 10⁻¹³	No overlap	SCZ:67 kb; UC:425 kb
PPP3CA	chr4:101,947 - 102,267	(5.0, 10.9)	Putamen basal ganglia	SCZ, CD	SCZ: - CD: Colon transversum	-4.87	-6.79	-2.96	1.57 × 10⁻⁶	1.28 × 10⁻¹⁰	5.54 × 10⁻³	No overlap	SCZ:280 kb; CD:384 kb

Gene overlap analysis of TWAS results from multiple-gene-conditioned fine-mapping analysis (Single-tissue_conditional; Supplementary Data 12, with detailed results in Supplementary Data 3) identified three common TWAS susceptibility genes (NR5A2, PPP3CA, SATB2) that meet the transcriptome-wide significance threshold (P_conditional < 3.20 × 10⁻⁶ for each disease separately; for diseases listed in the “Diseases primary tissue(s)” column). These three genes are shared between psychiatric and immune phenotypes in the same tissues and across the brain and non-brain tissues (Fig. 3). Increased predicted expression (indicated by a positive Z-score) of NR5A2 and SATB2 is associated with increased risk SCZ and CD as well as SCZ and UC. Decreased predicted expression (indicated by a negative Z-score) of PPP3CA is associated with increased risk for SCZ and CD. Genes inside the extended major histocompatibility complex (MHC; chr6:25-34 Mb) were excluded from gene overlap analysis.

Gene, susceptibility gene shared between psychiatric and immune disease(s); Gene-start-end, transcription start-end positions (including UTRs) in kilobases (genome build GRCh37/hg19); (h_med-min², h_med-max²), estimated minimum/maximum gene expression heritability in percentage attributable to SNPs in the vicinity of each gene (Methods) and averaged across 23 different tissues (Fig. 1); Primary tissue(s), primary tissue(s) identified from multiple-gene-conditioned fine-mapping analysis (Single-tissue_conditional, Methods), in which the transcriptome-wide significant gene-disease association signal occurred; Diseases primary tissue(s), diseases showing a transcriptome-wide association signal in the primary tissue(s) in Single-tissue_conditional analysis; CD, Crohn’s disease; UC, ulcerative colitis; SCZ, schizophrenia; Secondary tissue(s), further tissues with suggestive evidence (P_conditional < 1 × 10⁻⁴) for gene-disease association; Z statistic, Z-score from analysis Single-tissue_conditional and/or GBJ_conditional for primary tissue(s), the plus/minus sign indicates increased/decreased predicted expression of these genes to be associated with increased disease risk, TWAS P_conditional, P value from multiple-gene-conditioned fine-mapping analyses Single-tissue_conditional and/or GBJ_conditional for primary tissue(s), P values’ significance threshold was 3.20 × 10⁻⁶; Overlap with GWAS locus, testing an overlap with locus boundaries of established GWAS loci from the latest fine-mapping GWAS studies for SCZ³¹ and CD/UC^32,33. Distance to GWAS locus, closest GWAS loci from literature for SCZ³¹, CD, and UC³³ within ± 1 Mb region around coordinates from column “Gene-start-end” (in kb; genome build GRCh37/hg19): SCZ: chr1:200,250-200,422 (1q32.1) with candidate genes LINC00862, ZNF281. CD/UC: chr1:200,803-201,092 (1q32.1) with candidate genes CAMSAP2, RPL34P6, MRO3HP3, KIF21B, GPR25, CACNA1S, C1orf106, ASCL5. UC: chr2:199,447-199,709 (2q33.1). SCZ: chr2:200,387-200,633 (2q33.1) with candidate genes FTCDNL1, LOC101927641. SCZ: chr2:200,536-201,310 (2q33.1) with candidate genes C2orf47, C2orf69, FTCDNL1, SPATS2L, TYW5. SCZ: chr4:102,547-103,389 (4q24) with candidate genes BANK1, SLC39A8. CD: chr4:102,651-103,144 (4q24) with candidate gene BANK1.