Zarei Parvin, Kamali Zoha, Keshteli Ammar Hassanzadeh, Sedeh Peyman Adibi, Vaez Ahmad
Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
J Med Signals Sens. 2025 Sep 1;15:27. doi: 10.4103/jmss.jmss_16_25. eCollection 2025.
While metabolic biomarkers are known to play a significant role in the development of ulcerative colitis (UC), the exact causal relationships between them remain uncertain and warrant further investigations. Here we report a bidirectional two-sample Mendelian randomization (MR) study to evaluate causal relationships between 503 blood metabolites and UC.
We used genome-wide association study (GWAS) data on blood metabolite levels from two separate studies on European individuals ( = 8299 and 24,925). In addition, for UC, we utilized GWAS data from the same ancestry, including 417,932 participants, comprising 5371 UC cases and 412,561 controls. We employed the inverse variance weighted method for our discovery stage of MR analyses. Then, we used other methods, including MR-Egger, weighted median, weighted mode, simple mode, MR-pleiotropy residual sum and outlier, heterogeneity, and pleiotropy tests for sensitivity analyses to further validate our findings and assess the robustness of our results.
Our study suggests that total lipids in small high-density lipoprotein levels (S.HDL.L) are marginal significant positive associated with the development of UC (odds ratio = 1.167, 95% confidence interval: 0.998-1.364, = 0.051). In addition, UC did not have a statistically significant effect on the metabolites.
Total lipids in S.HDL.L may offer a potential trend as valuable circulating metabolic biomarkers for the screening and prevention of UC in clinical practice. In addition, they could serve as potential candidate molecules for elucidating the mechanisms underlying UC and for identifying suitable drug targets.
虽然已知代谢生物标志物在溃疡性结肠炎（UC）的发展中起重要作用，但它们之间的确切因果关系仍不确定，值得进一步研究。在此，我们报告一项双向两样本孟德尔随机化（MR）研究，以评估503种血液代谢物与UC之间的因果关系。
我们使用了来自两项针对欧洲个体的独立研究（样本量分别为8299和24925）的全基因组关联研究（GWAS）数据，这些数据涉及血液代谢物水平。此外，对于UC，我们利用了来自相同祖先的GWAS数据，包括417932名参与者，其中有5371例UC病例和412561例对照。我们在MR分析的发现阶段采用了逆方差加权法。然后，我们使用了其他方法，包括MR-Egger法、加权中位数法、加权众数法、简单众数法、MR多效性残差和离群值法、异质性检验和多效性检验进行敏感性分析，以进一步验证我们的发现并评估结果的稳健性。
我们的研究表明，小高密度脂蛋白水平（S.HDL.L）中的总脂质与UC的发生呈边缘显著正相关（优势比 = 1.167，95%置信区间：0.998 - 1.364，P = 0.051）。此外，UC对这些代谢物没有统计学上的显著影响。
S.HDL.L中的总脂质可能为临床实践中UC的筛查和预防提供有价值的循环代谢生物标志物的潜在趋势。此外，它们可以作为潜在的候选分子，用于阐明UC的潜在机制和确定合适的药物靶点。
