An atlas of the shared genetic architecture between atopic and gastrointestinal diseases
Abstract Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related tra...
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| Format: | Article |
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07416-7 |
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| author | Cancan Qi An Li Fengyuan Su Yu Wang Longyuan Zhou Ce Tang Rui Feng Ren Mao Minhu Chen Lianmin Chen Gerard H. Koppelman Arno R. Bourgonje Hongwei Zhou Shixian Hu |
| author_facet | Cancan Qi An Li Fengyuan Su Yu Wang Longyuan Zhou Ce Tang Rui Feng Ren Mao Minhu Chen Lianmin Chen Gerard H. Koppelman Arno R. Bourgonje Hongwei Zhou Shixian Hu |
| author_sort | Cancan Qi |
| collection | DOAJ |
| description | Abstract Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn’s disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4+ T cells consistently across relevant tissues. Fourteen genes are associated with comorbidities, with three genes are known treatment targets, showing probabilities for drug repurposing. Lower expressions of WDR18 and GPX4 in PBMC CD4+ T cells predict decreased risk of CD and asthma, which could be novel drug targets. MR unveils certain ADs led to higher risk of GIDs or vice versa. Taken together, here we show distinct genetic correlations between AD-GID pairs, but the correlated genomic loci converge on the dysregulation of CD4+ T cells. Inhibiting WDR18 and GPX4 expressions might be candidate therapeutic strategies for CD and asthma. Estimated causality indicates potential guidance for preventing comorbidity. |
| format | Article |
| id | doaj-art-c523e4402d0146ef8ce0ae1067ca2d2b |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c523e4402d0146ef8ce0ae1067ca2d2b2025-08-20T02:43:25ZengNature PortfolioCommunications Biology2399-36422024-12-017111110.1038/s42003-024-07416-7An atlas of the shared genetic architecture between atopic and gastrointestinal diseasesCancan Qi0An Li1Fengyuan Su2Yu Wang3Longyuan Zhou4Ce Tang5Rui Feng6Ren Mao7Minhu Chen8Lianmin Chen9Gerard H. Koppelman10Arno R. Bourgonje11Hongwei Zhou12Shixian Hu13Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Periodontology, Stomatological Hospital, Southern Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical UniversityUniversity of Groningen University Medical Centre Groningen, Groningen Research Institute for Asthma and COPDDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of GroningenMicrobiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen UniversityAbstract Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn’s disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4+ T cells consistently across relevant tissues. Fourteen genes are associated with comorbidities, with three genes are known treatment targets, showing probabilities for drug repurposing. Lower expressions of WDR18 and GPX4 in PBMC CD4+ T cells predict decreased risk of CD and asthma, which could be novel drug targets. MR unveils certain ADs led to higher risk of GIDs or vice versa. Taken together, here we show distinct genetic correlations between AD-GID pairs, but the correlated genomic loci converge on the dysregulation of CD4+ T cells. Inhibiting WDR18 and GPX4 expressions might be candidate therapeutic strategies for CD and asthma. Estimated causality indicates potential guidance for preventing comorbidity.https://doi.org/10.1038/s42003-024-07416-7 |
| spellingShingle | Cancan Qi An Li Fengyuan Su Yu Wang Longyuan Zhou Ce Tang Rui Feng Ren Mao Minhu Chen Lianmin Chen Gerard H. Koppelman Arno R. Bourgonje Hongwei Zhou Shixian Hu An atlas of the shared genetic architecture between atopic and gastrointestinal diseases Communications Biology |
| title | An atlas of the shared genetic architecture between atopic and gastrointestinal diseases |
| title_full | An atlas of the shared genetic architecture between atopic and gastrointestinal diseases |
| title_fullStr | An atlas of the shared genetic architecture between atopic and gastrointestinal diseases |
| title_full_unstemmed | An atlas of the shared genetic architecture between atopic and gastrointestinal diseases |
| title_short | An atlas of the shared genetic architecture between atopic and gastrointestinal diseases |
| title_sort | atlas of the shared genetic architecture between atopic and gastrointestinal diseases |
| url | https://doi.org/10.1038/s42003-024-07416-7 |
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