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METABOLIC SYNDROME / CLINICAL RESEARCH
Association between metabolic syndrome and inflammatory bowel disease: a bidirectional two-sample Mendelian randomized study
1
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China
2
Yuebei People’s Hospital of Shantou University Medical College, Shaoguan, China
3
Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
4
Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
These authors had equal contribution to this work
Submission date: 2025-01-25
Final revision date: 2025-07-19
Acceptance date: 2025-08-03
Online publication date: 2025-10-05
Corresponding author
Xiaowei Sun
Guangdong Provincial Key Laboratory of Gastroenterology Department of Gastroenterology Institute of Gastroenterology of Guangdong Province Nanfang Hospital Southern Medical University Guangzhou, China
Guangdong Provincial Key Laboratory of Gastroenterology Department of Gastroenterology Institute of Gastroenterology of Guangdong Province Nanfang Hospital Southern Medical University Guangzhou, China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Epidemiological studies have revealed parallel increases in the incidences of metabolic syndrome (MetS) and inflammatory bowel disease (IBD). Clinical observational studies have shown an association between MetS and a poor prognosis of IBD. However, the causal relationship between MetS and IBD remains unclear. This study used bidirectional two-sample Mendelian randomization to investigate potential causal links between MetS and IBD, including ulcerative colitis (UC) and Crohn’s disease (CD).
Material and methods:
Genetic associations of MetS and its components with IBD were sourced from public databases of European populations. Inverse variance weighting was conducted, with weighted median, Mendelian randomization–Egger (MR-Egger), and Mendelian randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods used as sensitivity analyses. This process was repeated in the opposite direction.
Results:
The inverse variance weighted (IVW) method showed that genetic prediction of MetS may be a potential risk factor for CD (OR = 1.34, 95% CI: 1.009–1.779; p = 0.043). In further estimating the different components of MetS, it was found that waist circumference may increase the risk of CD (OR = 1.33, 95% CI: 1.05–1.684; p = 0.018) and hypertension may increase the risk of UC (OR = 1.61, 95% CI: 1.084–2.39; p = 0.018). Reverse analysis showed that IBD may increase triglyceride levels (OR = 1.019, 95% CI: 1.000–1.038; p = 0.049).
Conclusions:
This MR analysis showed a causal relationship between genetically predicted MetS and CD, and genetically predicted hypertension and UC. Therefore, these patients need to be closely monitored clinically for the risk of CD/UC comorbidities. In patients with IBD, close monitoring of MetS-associated cardiovascular risk is required.
Epidemiological studies have revealed parallel increases in the incidences of metabolic syndrome (MetS) and inflammatory bowel disease (IBD). Clinical observational studies have shown an association between MetS and a poor prognosis of IBD. However, the causal relationship between MetS and IBD remains unclear. This study used bidirectional two-sample Mendelian randomization to investigate potential causal links between MetS and IBD, including ulcerative colitis (UC) and Crohn’s disease (CD).
Material and methods:
Genetic associations of MetS and its components with IBD were sourced from public databases of European populations. Inverse variance weighting was conducted, with weighted median, Mendelian randomization–Egger (MR-Egger), and Mendelian randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods used as sensitivity analyses. This process was repeated in the opposite direction.
Results:
The inverse variance weighted (IVW) method showed that genetic prediction of MetS may be a potential risk factor for CD (OR = 1.34, 95% CI: 1.009–1.779; p = 0.043). In further estimating the different components of MetS, it was found that waist circumference may increase the risk of CD (OR = 1.33, 95% CI: 1.05–1.684; p = 0.018) and hypertension may increase the risk of UC (OR = 1.61, 95% CI: 1.084–2.39; p = 0.018). Reverse analysis showed that IBD may increase triglyceride levels (OR = 1.019, 95% CI: 1.000–1.038; p = 0.049).
Conclusions:
This MR analysis showed a causal relationship between genetically predicted MetS and CD, and genetically predicted hypertension and UC. Therefore, these patients need to be closely monitored clinically for the risk of CD/UC comorbidities. In patients with IBD, close monitoring of MetS-associated cardiovascular risk is required.
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