Causal Relationship Between Glucose and Inflammatory Bowel Disease: A
Bidirectional Two-Sample Mendelian Randomization Study
Abstract
Abstract Background Association between glucose and inflammatory bowel
disease (IBD) was found in previous observational studies and in cohort
studies. However, it is not clear whether these associations reflect
causality. Thus, this study investigated whether there is such a causal
relation between elevated glucose and IBD, Crohn’s disease (CD) and
ulcerative colitis (UC). Methods We performed a two-sample Mendelian
Randomization (MR) with the independent genetic instruments identified
from the largest available genome-wide association study (GWAS) for IBD
(5,673 cases; 213,119 controls) and its main subtypes, CD and UC.
Summarized data for glucose which included 200,622 cases and glycemic
traits including HbA1c and type 2 diabetes(T2DM) were obtained from
different GWAS studies. Primary and secondary analyses were conducted by
preferentially using the radial inverse-variance weighted (IVW)
approach. A number of other meta-analysis approach and sensitivity
analyses were carried out to assess the robustness of the results.
Results We did not find a causal effect of genetically predicted glucose
on IBD as a whole (OR 0.858; 95% CI 0.649-1.135; P = 0.286). In subtype
analyses glucose was also suggestively not associated with Crohn’s
disease (OR 0.22; 95% CI 0.04-1.00; P = 0.05) and ulcerative colitis(OR
0.940; 95% CI 0.628-1.407; P = 0.762). In the other direction, IBD and
it’s subtypes were not related to glucose and glycemic traits.
Conclusions This MR study is not providing any evidence for a causal
relationship between genetically predicted elevated glucose and IBD as
well as it’s subtypes UC and CD. Regarding the other direction, no
causal associations could be found. Future studies with robust genetic
instruments are needed to confirm this conclusion.