Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus
Abstract Inflammatory bowel disease (IBD) is an autoimmune disease (AD) characterized by chronic, relapsing intestinal inflammation. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement and overactivation of both innate and adaptive immunity. The extra inte...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-98991-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850206597116067840 |
|---|---|
| author | Vikram R. Shaw Jinyoung Byun Catherine Zhu Rowland W. Pettit Jeffrey M. Cohen Younghun Han Christopher I. Amos |
| author_facet | Vikram R. Shaw Jinyoung Byun Catherine Zhu Rowland W. Pettit Jeffrey M. Cohen Younghun Han Christopher I. Amos |
| author_sort | Vikram R. Shaw |
| collection | DOAJ |
| description | Abstract Inflammatory bowel disease (IBD) is an autoimmune disease (AD) characterized by chronic, relapsing intestinal inflammation. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement and overactivation of both innate and adaptive immunity. The extra intestinal manifestations (EIMs) that commonly occur in IBD include many of the organ sites that are affected by SLE. ADs are often comorbid with one another and may have shared underlying genetic features and architectures contributing to their pathogenesis and disease course. We performed both epidemiological and post-genome wide association study (GWAS) analyses to investigate the shared genetic features between IBD and systemic lupus erythematosus (SLE). Specifically, we performed epidemiological association analysis in the All of Us Research Program (AoURP) and genome-wide/local genetic correlation analysis and cell-type specific SNP heritability enrichment analysis using previously published summary level data. A significant epidemiologic association exists between IBD and SLE with an adjusted odds ratio (aOR) of 2.94 (95% CI: 2.45–3.53; P < 0.001) in a multivariable model accounting for confounders in the AoURP data. Genome-wide genetic correlation analysis in previously published summary level data demonstrated a significant genetic correlation between IBD, CD, and UC with SLE, and local genetic correlation analysis demonstrated several positive and significant correlations in local genomic regions harboring disease variants in genes common to both SLE and IBD etiology, including variants in ELF1, CD226, JAZF1, WDFY4, and JAK2. Cell-type SNP heritability enrichment analysis identified both overlapping and distinct functional categories contributing to SNP heritability across IBD phenotypes. Notably, IBD-related phenotypes demonstrated significant enrichment in T-lymphocyte functional groups while SLE signal appeared in distinct categories, such as B-lymphocytes (along with CD). Gene-level collapsing analysis of rare variants in the United Kingdom BioBank (UKBB) identified overlapping nominally-significant genes between SLE and IBD, CD, and UC. By leveraging several post-GWAS methods, the present study identifies shared genetic features between IBD and SLE, highlighting similarities and differences in the genetic features that contribute to the pathogenesis of each disease. |
| format | Article |
| id | doaj-art-985e1660e2a24daabef823a7bed460d6 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-985e1660e2a24daabef823a7bed460d62025-08-20T02:10:46ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-98991-0Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosusVikram R. Shaw0Jinyoung Byun1Catherine Zhu2Rowland W. Pettit3Jeffrey M. Cohen4Younghun Han5Christopher I. Amos6Institute for Clinical and Translational Research, Baylor College of MedicineDepartment of Internal Medicine, University of New Mexico Health Science CenterInstitute for Clinical and Translational Research, Baylor College of MedicineDepartment of Pathology, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Dermatology, Yale School of MedicineDepartment of Internal Medicine, University of New Mexico Health Science CenterInstitute for Clinical and Translational Research, Baylor College of MedicineAbstract Inflammatory bowel disease (IBD) is an autoimmune disease (AD) characterized by chronic, relapsing intestinal inflammation. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement and overactivation of both innate and adaptive immunity. The extra intestinal manifestations (EIMs) that commonly occur in IBD include many of the organ sites that are affected by SLE. ADs are often comorbid with one another and may have shared underlying genetic features and architectures contributing to their pathogenesis and disease course. We performed both epidemiological and post-genome wide association study (GWAS) analyses to investigate the shared genetic features between IBD and systemic lupus erythematosus (SLE). Specifically, we performed epidemiological association analysis in the All of Us Research Program (AoURP) and genome-wide/local genetic correlation analysis and cell-type specific SNP heritability enrichment analysis using previously published summary level data. A significant epidemiologic association exists between IBD and SLE with an adjusted odds ratio (aOR) of 2.94 (95% CI: 2.45–3.53; P < 0.001) in a multivariable model accounting for confounders in the AoURP data. Genome-wide genetic correlation analysis in previously published summary level data demonstrated a significant genetic correlation between IBD, CD, and UC with SLE, and local genetic correlation analysis demonstrated several positive and significant correlations in local genomic regions harboring disease variants in genes common to both SLE and IBD etiology, including variants in ELF1, CD226, JAZF1, WDFY4, and JAK2. Cell-type SNP heritability enrichment analysis identified both overlapping and distinct functional categories contributing to SNP heritability across IBD phenotypes. Notably, IBD-related phenotypes demonstrated significant enrichment in T-lymphocyte functional groups while SLE signal appeared in distinct categories, such as B-lymphocytes (along with CD). Gene-level collapsing analysis of rare variants in the United Kingdom BioBank (UKBB) identified overlapping nominally-significant genes between SLE and IBD, CD, and UC. By leveraging several post-GWAS methods, the present study identifies shared genetic features between IBD and SLE, highlighting similarities and differences in the genetic features that contribute to the pathogenesis of each disease.https://doi.org/10.1038/s41598-025-98991-0Inflammatory bowel diseaseAutoimmune diseaseSystemic lupus erythematosus |
| spellingShingle | Vikram R. Shaw Jinyoung Byun Catherine Zhu Rowland W. Pettit Jeffrey M. Cohen Younghun Han Christopher I. Amos Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus Scientific Reports Inflammatory bowel disease Autoimmune disease Systemic lupus erythematosus |
| title | Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus |
| title_full | Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus |
| title_fullStr | Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus |
| title_full_unstemmed | Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus |
| title_short | Uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus |
| title_sort | uncovering shared genetic features between inflammatory bowel disease and systemic lupus erythematosus |
| topic | Inflammatory bowel disease Autoimmune disease Systemic lupus erythematosus |
| url | https://doi.org/10.1038/s41598-025-98991-0 |
| work_keys_str_mv | AT vikramrshaw uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus AT jinyoungbyun uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus AT catherinezhu uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus AT rowlandwpettit uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus AT jeffreymcohen uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus AT younghunhan uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus AT christopheriamos uncoveringsharedgeneticfeaturesbetweeninflammatoryboweldiseaseandsystemiclupuserythematosus |