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Inflammatory Bowel Disease and Risk of Global Cardiovascular Diseases and Type 2 Diabetes
Zhengbao Zhu1,2, Yiming Jia1, Fu-Rong Li3
1Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China.
Insights
Inflammatory bowel disease (IBD) shows observational links to cardiometabolic diseases. However, genetic analyses indicate no causal relationship between Crohn's disease (CD) or ulcerative colitis (UC) and increased cardiometabolic risk.
Area of Science:
- Gastroenterology and Cardiology
- Genetic Epidemiology
Background:
- Observational studies suggest a link between inflammatory bowel disease (IBD) and increased cardiometabolic disease risk.
- IBD encompasses Crohn's disease (CD) and ulcerative colitis (UC).
- Cardiometabolic diseases include heart failure, type 2 diabetes, myocardial infarction, and ischemic stroke.
Purpose of the Study:
- To investigate the observational and genetic associations between CD and UC and cardiometabolic outcomes.
- To determine if the observed associations between IBD and cardiometabolic diseases are causal.
Main Methods:
- Phenotypic and genetic association analyses using UK Biobank data (over 400,000 participants).
- Mendelian randomization (MR) analyses employing single nucleotide polymorphisms for CD (415) and UC (273) as genetic instruments.
- Utilizing summary-level data from genome-wide association studies (GWAS) for cardiometabolic outcomes (over 2.2 million participants).
Main Results:
- Observational analyses revealed associations between CD and higher risks of heart failure and type 2 diabetes.
- Ulcerative colitis (UC) was linked to increased risks of all assessed cardiometabolic diseases.
- Genetic risk scores and MR analyses did not support a causal link between CD or UC and cardiometabolic diseases.
Conclusions:
- While observational data show associations between IBD and cardiometabolic diseases, a causal relationship is not supported.
- The findings suggest that factors other than a direct causal link may explain the observed associations.
- Further research is needed to elucidate the complex interplay between IBD and cardiometabolic health.
Background:
Inflammatory bowel disease (IBD) was associated with elevated risk of cardiometabolic diseases in observational studies. We aimed to evaluate the observational and genetic associations of Crohn's disease (CD) and ulcerative colitis (UC) with multiple cardiometabolic outcomes.
Methods:
Our phenotypic and genetic association analyses included more than 400 000 participants who were free of major cardiovascular disease and diabetes at recruitment (2006-2010) and were followed up until December 2019 based on the UK Biobank. For the Mendelian randomization (MR) analyses, 415 and 273 single nucleotide polymorphisms associated with CD and UC, respectively, were selected as genetic instruments. Summary-level data on individual cardiometabolic outcomes were obtained from 4 different genome-wide association studies with a total of 2 248 842 participants.
Results:
In the multivariable-adjusted observational analyses, CD was associated with higher risks of heart failure (hazard ratio [HR], 1.72; 95% confidence interval, 1.22-2.42) and type 2 diabetes (HR, 2.11; 95% confidence interval, 1.67-2.67) but not with myocardial infarction or ischemic stroke. UC was related to increased risks of all the assessed cardiometabolic diseases (HRs ranged from 1.29 for myocardial infarction to 1.76 for type 2 diabetes). Conversely, neither the genetic risk score for CD nor that for UC was associated with higher risk of developing cardiometabolic diseases. In 2-sample MR analyses, genetically determined CD and UC were not associated with any of the assessed cardiometabolic diseases (all P values >.05).
Conclusions:
Despite confirming the observational associations, our study does not support a causal association between IBD and elevated risk of cardiometabolic diseases.
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