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.

From: Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease

Gene

Gene-start-end (in kb)

(hmed-min2, hmed-max2) in %

Primary tissue(s) of strongest gene-disease association

Diseases primary tissue(s)

Secondary tissue(s) of gene-disease association

Zmarginal primary tissue

Pconditional primary tissue

Overlap with GWAS locus

Distance to GWAS locus

SCZ

CD

UC

SCZ

CD

UC

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

  1. Gene overlap analysis of TWAS results from multiple-gene-conditioned fine-mapping analysis (Single-tissueconditional; 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 (Pconditional < 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.
  2. 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); (hmed-min2, hmed-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-tissueconditional, 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-tissueconditional analysis; CD, Crohn’s disease; UC, ulcerative colitis; SCZ, schizophrenia; Secondary tissue(s), further tissues with suggestive evidence (Pconditional < 1 × 10−4) for gene-disease association; Z statistic, Z-score from analysis Single-tissueconditional and/or GBJconditional for primary tissue(s), the plus/minus sign indicates increased/decreased predicted expression of these genes to be associated with increased disease risk, TWAS Pconditional, P value from multiple-gene-conditioned fine-mapping analyses Single-tissueconditional and/or GBJconditional 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/UC32,33. 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.
Back to article page