The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study
Background. While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods. Mendelian randomization (MR) was employed to invest...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2024-01-01
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| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2024/1266139 |
| _version_ | 1797245064419737600 |
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| author | Shu Zhou Qi Sun Ning Gao Zekai Hu Junjun Jia Jiangwei Song Guocong Xu Aiqiang Dong Weiliang Xia Jiafeng Wu |
| author_facet | Shu Zhou Qi Sun Ning Gao Zekai Hu Junjun Jia Jiangwei Song Guocong Xu Aiqiang Dong Weiliang Xia Jiafeng Wu |
| author_sort | Shu Zhou |
| collection | DOAJ |
| description | Background. While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods. Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn’s disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10−8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Results. Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03–1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03–1.11; (p<0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03–1.25; p=0.01). Conclusions. The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD. |
| first_indexed | 2024-04-24T19:20:58Z |
| format | Article |
| id | doaj.art-932556ba685f4cb6bab28885806ab6df |
| institution | Directory Open Access Journal |
| issn | 2291-2797 |
| language | English |
| last_indexed | 2024-04-24T19:20:58Z |
| publishDate | 2024-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj.art-932556ba685f4cb6bab28885806ab6df2024-03-26T00:00:02ZengHindawi LimitedCanadian Journal of Gastroenterology and Hepatology2291-27972024-01-01202410.1155/2024/1266139The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized StudyShu Zhou0Qi Sun1Ning Gao2Zekai Hu3Junjun Jia4Jiangwei Song5Guocong Xu6Aiqiang Dong7Weiliang Xia8Jiafeng Wu9Hangzhou Ninth People’s HospitalHangzhou Ninth People’s HospitalDepartment of Cardiovascular SurgeryDivision of Hepatobiliary and Pancreatic SurgeryDivision of Hepatobiliary and Pancreatic SurgeryHangzhou Ninth People’s HospitalDepartment of Cardiovascular SurgeryDepartment of Cardiovascular SurgeryDivision of Hepatobiliary and Pancreatic SurgeryHangzhou Ninth People’s HospitalBackground. While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods. Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn’s disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10−8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Results. Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03–1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03–1.11; (p<0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03–1.25; p=0.01). Conclusions. The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD.http://dx.doi.org/10.1155/2024/1266139 |
| spellingShingle | Shu Zhou Qi Sun Ning Gao Zekai Hu Junjun Jia Jiangwei Song Guocong Xu Aiqiang Dong Weiliang Xia Jiafeng Wu The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study Canadian Journal of Gastroenterology and Hepatology |
| title | The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study |
| title_full | The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study |
| title_fullStr | The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study |
| title_full_unstemmed | The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study |
| title_short | The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study |
| title_sort | role of inflammatory biomarkers in mediating the effect of inflammatory bowel disease on nonmalignant digestive system diseases a multivariable mendelian randomized study |
| url | http://dx.doi.org/10.1155/2024/1266139 |
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