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  4. Vol 6, Issue 1, 2025

Causal relationship between serum metabolites and Crohns disease: A bidirectional two-sample Mendelian randomization study

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DOI: 10.23977/medsc.2025.060110 | Downloads: 4 | Views: 100

Author(s)

Shuanghu Zhang 1, Shengli Huang 1, Liu Ye 2, Guanghua Yang 1, Changyou Wang 1

Affiliation(s)

1 Department of Gastrointestinal Oncology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei, 063000, China
2 Breast Disease Treatment Center, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei, 063000, China

Corresponding Author

Changyou Wang

ABSTRACT

A two-way two-sample Mendelian randomization (MR) approach was used to explore the causal relationship between serum metabolites and Crohn's disease. The summary data from Genome-Wide Association Studies (GWAS) were analyzed using single nucleotide polymorphisms (SNPs) loci closely related to Crohns disease as instrumental variables (IVs). The causal relationship between serum metabolites and Crohns disease was comprehensively evaluated using methods such as Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted Median Estimation (WME), Simple Mode (SM), and Weighted Mode (WM). The evaluation primarily focused on the P-value of IVW, odds ratio (OR), and 95% confidence intervals (CI). Respectively, the Cochran Q test for heterogeneity was performed using the IVW and MR-Egger methods, the pleiotropy test was conducted using the MR-Egger intercept method, and the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) method was used to identify outliers. Leave-one-out sensitivity analysis was conducted. Additionally, the reverse causality between Crohns disease and serum metabolites was analyzed using these five methods. The IVW results show that four known metabolites and one unknown metabolite are closely related to Crohns disease. Among them, homocitrulline { OR (95% CI): 0. 845 (0. 761 to 0. 939), P = 0. 002}, X-17325 { OR (95% CI): 0. 825 (0. 733 to 0. 928), P = 0. 001}, 1-palmitoyl-2-arachidonoyl-gpc { OR (95% CI): 0. 842 (0. 783 to 0. 906), P < 0. 001} were protective factors for Crohns disease; plasma lactate { OR (95% CI): 1. 308 (1. 112 to 1. 537),P = 0. 001}, the ratio of Oleoyl-linoleoyl-glycerol /linoleoyl-arachidonoyl-glycerol { OR (95% CI): 1. 206 (1. 115 to 1. 304), P < 0. 001} were risk factors for Crohns disease. The results of the reverse MR analysis showed that there is no reverse causal relationship between Crohns disease and homocitrulline, X-17325, 1-palmitoyl-2-arachidonoyl-gpc, plasma lactate, and the ratio of Oleoyl-linoleoyl-glycerol/linoleoyl-arachidonoyl-glycerol(P > 0. 05). Five serum metabolites have been identified to have a causal association with the risk of Crohns disease, providing new theoretical basis and practical guidance for the design of treatment regimens for Crohns diseas. 

KEYWORDS

Serum metabolites; Crohns disease; Mendelian randomization; Causal inference

CITE THIS PAPER

Shuanghu Zhang, Shengli Huang, Liu Ye, Guanghua Yang, Changyou Wang. Causal relationship between serum metabolites and Crohns disease: A bidirectional two-sample Mendelian randomization study. MEDS Clinical Medicine (2025) Vol. 6: 64-73. DOI: http://dx.doi.org/10.23977/medsc.2025.060110.

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