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. 2024 Sep 16;25(1):868.
doi: 10.1186/s12864-024-10787-0.

Investigating the shared genetic basis of inflammatory bowel disease and systemic lupus erythematosus using genetic overlap analysis

Weichao Yuan  1 , Qinghua Luo  2 , Na Wu  3   4
Affiliations

Investigating the shared genetic basis of inflammatory bowel disease and systemic lupus erythematosus using genetic overlap analysis

Weichao Yuan et al. BMC Genomics. .

Abstract

Background: Inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) are autoimmune diseases that often coexist clinically. This phenomenon might be due to shared genetic components.

Methods: Genome-wide association study (GWAS) data for IBD and SLE were analyzed to determine both global and local genetic correlations using three methodologies: linkage disequilibrium score regression (LDSC), genetic covariance analyzer (GNOVA), and SUPERGNOVA. The genetic overlap and risk loci were subsequently examined using the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework. Furthermore, a multi-trait analysis of MTAG was employed to validate the loci, followed by an LDSC analysis focusing on tissue-specific gene expression.

Results: GWAS findings demonstrated a marked global genetic correlation between IBD (including Crohn's disease and ulcerative colitis) and SLE. Locally, SLE showed a strong association with IBD and Crohn's disease on chromosomes 10, 19, and 22. ConjFDR analysis confirmed the genetic overlap and identified relevant genetic risk loci. MTAG further validated several shared susceptibility genes. Additionally, the LDSC-SEG analysis results indicate that IBD (including CD and UC) and SLE are jointly enriched in the tissues of Spleen and Whole Blood.

Conclusion: This study confirms a genetic overlap between IBD and SLE, identifying marked comorbid genes and offering new insights for treating these diseases.

Keywords: Genetic overlap; Genetic risk loci; Genetic structure; Inflammatory bowel disease; Systemic lupus erythematosus.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Conditional quantile-quantile plot. The dashed line indicates the expected line under the null hypothesis, and the deflection to the left indicates the degree of pleiotropic enrichment. (A) IBD-SLE. (B) SLE-IBD. (C) CD-SLE. (D) SLE-CD. (E) UC-SLE. (F) SLE-UC.SLE, Systemic Lupus Erythematosus; IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis
Fig. 2
Fig. 2
(A) ConjFDR Manhattan plot of IBD and SLE. (B) ConjFDR Manhattan plot of CD and SLE. (C) ConjFDR Manhattan plot of UC and SLE.The shared risk loci between SLE and IBD, CD and UC were marked. The statistically significant causality is defined to be conjFDR < 0.05. SLE, Systemic Lupus Erythematosus; IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis
Fig. 3
Fig. 3
(A) Manhattan map of genetic risk loci for IBD and SLE by MTAG. (B) Intersection gene map of IBD and SLE after conjfdr and MTAG analysis. (C) Gene-gene interaction network of comorbidity genes between IBD and SLE.SLE, Systemic Lupus Erythematosus; IBD, inflammatory bowel disease
Fig. 4
Fig. 4
(A) Manhattan map of genetic risk loci for CD and SLE by MTAG. (B) Intersection gene map of CD and SLE after conjfdr and MTAG analysis. (C) Gene-gene interaction network of comorbidity genes between CD and SLE.SLE, Systemic Lupus Erythematosus; CD, Crohn’s disease
Fig. 5
Fig. 5
(A) Manhattan map of genetic risk loci for UC and SLE by MTAG. (B) Intersection gene map of UC and SLE after conjfdr and MTAG analysis. (C) Gene-gene interaction network of comorbidity genes between UC and SLE.SLE, Systemic Lupus Erythematosus; UC, ulcerative colitis
Fig. 6
Fig. 6
Tissues enrichment results of IBD (A), SLE (B), CD (C), and UC (D) using gene expression data of 53 tissues from GTEx.SLE, Systemic Lupus Erythematosus; IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis
Fig. 7
Fig. 7
The tissue expression analysis of MAGMA was obtained by MTAG. (A) SLE-IBD. (B) SLE-CD. (C) SLE-UC.SLE, Systemic Lupus Erythematosus; IBD, inflammatory bowel disease; CD, Crohn’s disease; UC, ulcerative colitis
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