Causality of serum metabolites on ulcerative colitis: a two-sample Mendelian randomization study
10.3760/cma.j.cn115822-20240326-00057
- VernacularTitle:血清代谢物与溃疡性结肠炎的因果关系：一项两样本孟德尔随机化研究
- Author:
Yun MA
1
;
Xingyu JI
;
Dan DOU
;
Shuqing WANG
;
Yanzhen LIU
;
Shengsheng ZHANG
;
Luqing ZHAO
Author Information
1. 北京中医药大学，北京 100029
- Publication Type:Journal Article
- Keywords:
Ulcerative colitis;
Mendelian randomization;
Blood metabolites;
Gene determination of metabolites
- From:
Chinese Journal of Clinical Nutrition
2025;33(1):31-39
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect and causality of serum metabolites on the pathogenesis of ulcerative colitis (UC), so as to provide reference for nutritional programs for patients with UC.Methods:Two-sample Mendelian randomization (MR) analysis was performed to estimate the causal relationship between serum metabolites and UC. Genome-wide association studies (GWAS) of 1 400 metabolites were performed, with the metabolites as exposure and UC as outcome. Inverse-variance weighted (IVW) was used to calculate causal estimates. Four other MR methods with different modeling assumptions including MR-Egger, weighted median, weighted mode, and simple mode were used as additional analyses to improve the stability of the results. The results were validated through heterogeneity and pleiotropy tests. Finally, the possible causal metabolites were analyzed by metabolic pathway analysis.Results:MR analysis revealed that 85 metabolites had a possible causal relationship with UC. Among them, phosphatidylglycerol 1,2-dipalmitoyl-gpc (DPPC) ( P=2.75×10 -6) and isovaleryl carnitine (C5) ( P=1.84×10 -5) were significant risk factors for UC. Metabolic pathway analysis identified 5 metabolic pathways that might be affected by these metabolites (all P<0.05), among which the porphyrin ( P=0.004) and pyrimidine metabolic pathways ( P=0.008) had higher confidence in impacting UC. Conclusions:There are causal relationships between some serum metabolites (in particular 1,2-dipalmitoyl-GPC and isovalerylcarnitine) and the risk of UC. The porphyrin and pyrimidine metabolic pathways may impact the pathogenesis of UC.
