Key result
Genetically determined total cholesterol was causally associated with a reduced risk of ulcerative colitis (OR 0.674; 95% CI 0.554-0.820; p<0.00625).
Why the study?
Observational studies have recognized associations between blood lipid traits and inflammatory bowel diseases, but whether these associations are causal remains unclear.
Do genetically determined blood lipid traits causally affect the risk of inflammatory bowel diseases?
Observational
Do genetically determined blood lipid traits causally affect the risk of inflammatory bowel diseases?
Odds Ratio: 0.674 (95% CI 0.554–0.82)
p-value: p=< 0.00625
Genetically determined total cholesterol and LDL-C are causally associated with a reduced risk of ulcerative colitis, providing insights into the metabolic regulation of IBDs.
May suggest causal lipid-IBD links; leaves open confirmation before any clinical inference.
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), have become a global health problem with a rapid growth of incidence in newly industrialized countries. Observational studies have recognized associations between blood lipid traits and IBDs, but the causality still remains unclear. To determine the causal effects of blood lipid traits, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) on IBDs, two-sample Mendelian randomization (MR) analyses were conducted using the summary-level genome-wide association study (GWAS) statistics of blood lipid traits and IBDs. Our univariable MR using multiplicative random-effect inverse-variance weight (IVW) method identified TC (OR: 0.674; 95% CI: 0.554, 0.820; p < 0.00625) and LDL-C (OR: 0.685; 95% CI: 0.546, 0.858; p < 0.00625) as protective factors of UC. The result of our multivariable MR analysis further provided suggestive evidence of the protective effect of TC on UC risk (OR: 0.147; 95% CI: 0.025, 0.883; p < 0.05). Finally, our MR-BMA analysis prioritized TG (MIP: 0.336; θ^MACE: −0.025; PP: 0.31; θ^λ: −0.072) and HDL-C (MIP: 0.254; θ^MACE: −0.011; PP: 0.232; θ^λ: −0.04) for CD and TC (MIP: 0.721; θ^MACE: −0.257; PP: 0.648; θ^λ: −0.356) and LDL-C (MIP: 0.31; θ^MACE: −0.095; PP: 0.256; θ^λ: −0.344) for UC as the top-ranked protective factors. In conclusion, the causal effect of TC for UC prevention was robust across all of our MR approaches, which provide the first evidence that genetically determined TC is causally associated with reduced risk of UC. The finding of this study provides important insights into the metabolic regulation of IBDs and potential metabolites targeting strategies for IBDs intervention.
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Yao et al. (2023) conducted an observational in Inflammatory bowel diseases (Crohn's disease and ulcerative colitis). Blood lipid traits (Total cholesterol, LDL-C, TG, HDL-C) was evaluated on Ulcerative colitis (OR 0.674, 95% CI 0.554, 0.820, p=< 0.00625). Genetically determined total cholesterol was causally associated with a reduced risk of ulcerative colitis (OR 0.674; 95% CI 0.554-0.820; p<0.00625).
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