Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders
Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genet...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/97663 |
| _version_ | 1848766299394539520 |
|---|---|
| author | Adewuyi, Emmanuel Porter, T. O’Brien, E.K. Olaniru, O. Verdile, Giuseppe Laws, S.M. |
| author_facet | Adewuyi, Emmanuel Porter, T. O’Brien, E.K. Olaniru, O. Verdile, Giuseppe Laws, S.M. |
| author_sort | Adewuyi, Emmanuel |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and bidirectionally with GERD. Gene-based analyses reveal a gene-level genetic overlap between T2D and GI disorders and identify several shared genes reaching genome-wide significance. Pathway-based study implicates leptin (T2D – IBD), thyroid, interferon, and notch signalling (T2D – IBS), abnormal circulating calcium (T2D – PUD), cardiovascular, viral, proinflammatory and (auto)immune-mediated mechanisms in T2D and GI disorders. These findings support a risk-increasing genetic overlap between T2D and GI disorders (except IBD), implicate shared biological pathways with putative causality for certain T2D – GI pairs, and identify targets for further investigation. |
| first_indexed | 2025-11-14T11:48:56Z |
| format | Journal Article |
| id | curtin-20.500.11937-97663 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:48:56Z |
| publishDate | 2024 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-976632025-05-03T08:11:12Z Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders Adewuyi, Emmanuel Porter, T. O’Brien, E.K. Olaniru, O. Verdile, Giuseppe Laws, S.M. Diabetes Mellitus, Type 2 Humans Genome-Wide Association Study Gastrointestinal Diseases Genetic Predisposition to Disease Mendelian Randomization Analysis Humans Gastrointestinal Diseases Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Genome-Wide Association Study Mendelian Randomization Analysis Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and bidirectionally with GERD. Gene-based analyses reveal a gene-level genetic overlap between T2D and GI disorders and identify several shared genes reaching genome-wide significance. Pathway-based study implicates leptin (T2D – IBD), thyroid, interferon, and notch signalling (T2D – IBS), abnormal circulating calcium (T2D – PUD), cardiovascular, viral, proinflammatory and (auto)immune-mediated mechanisms in T2D and GI disorders. These findings support a risk-increasing genetic overlap between T2D and GI disorders (except IBD), implicate shared biological pathways with putative causality for certain T2D – GI pairs, and identify targets for further investigation. 2024 Journal Article http://hdl.handle.net/20.500.11937/97663 10.1038/s42003-024-06333-z eng unknown |
| spellingShingle | Diabetes Mellitus, Type 2 Humans Genome-Wide Association Study Gastrointestinal Diseases Genetic Predisposition to Disease Mendelian Randomization Analysis Humans Gastrointestinal Diseases Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Genome-Wide Association Study Mendelian Randomization Analysis Adewuyi, Emmanuel Porter, T. O’Brien, E.K. Olaniru, O. Verdile, Giuseppe Laws, S.M. Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| title | Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| title_full | Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| title_fullStr | Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| title_full_unstemmed | Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| title_short | Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| title_sort | genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders |
| topic | Diabetes Mellitus, Type 2 Humans Genome-Wide Association Study Gastrointestinal Diseases Genetic Predisposition to Disease Mendelian Randomization Analysis Humans Gastrointestinal Diseases Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Genome-Wide Association Study Mendelian Randomization Analysis |
| url | http://hdl.handle.net/20.500.11937/97663 |