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GASTROENTEROLOGY / RESEARCH PAPER
The causal effects of genetically determined 1400 human blood metabolites and metabolite ratios on the risk of gastrointestinal tumors：a Mendelian randomization study
1
Qinghai University Affiliated Hospital (The Clinical Medical School), Qinghai University, China
2
Department of Oncology, Affiliated Hospital of Qinghai University,, China
3
Gansu Corps Hospital of CAPF, China
These authors had equal contribution to this work
Submission date: 2025-02-21
Final revision date: 2025-04-29
Acceptance date: 2025-05-04
Online publication date: 2025-06-22
Corresponding author
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Recently, studies investigating the connection between blood metabolites and gastrointestinal tumors have gained increased attention. A Mendelian randomization (MR) study is considered the second most persuasive research method to explore the causal relationship between exposure and outcome after RCT.
Material and methods:
This analysis utilized the inverse variance weighted (IVW) method, the weighted median (WM) method, and MR-Egger regression. Initially, we analyzed GWAS data from the FinnGen database to identify various metabolites and their ratios. Subsequently, we repeatedly analyzed GWAS data from the Open GWAS database to filter out duplicate results.
Results:
5-methyluridine [FinnGen : odds ratio (OR) =1.16, 95% confidence interval (CI) =1.02-1.31, P=0.03, FDR-P=0.04; Open GWAS: OR=1.08, 95%CI=1.01-1.17, P=0.03, FDR-P=0.04] and 1-dihomo-linolenylglycerol (FinnGen: OR=1.30, 95%CI=1.02-1.65, P=0.03, FDR-P=0.04; Open GWAS: OR=1.16, 95%CI=1.02-1.31, P=0.03, FDR-P=0.04) are positively associated with the risk of gastric cancer (GC). Sphingomyelin (FinnGen: OR=0.73, 95%CI=0.54-0.98, P=0.04, FDR-P=0.04; Open GWAS: OR=0.81, 95%CI=0.67-0.97, P=0.02, FDR-P=0.04) is negatively correlated with GC risk. Carnitine to propionylcarnitine (C3) ratio (FinnGen: OR=1.11, 95%CI=1.01-1.22, P=0.03, FDR-P=0.04; Open GWAS: OR=1.07, 95%CI=1.01-1.14, P=0.04, FDR-P=0.04), Arachidonate to linoleate ratio (FinnGen: OR=1.10, 95%CI=1.02-1.19, P=0.02, FDR-P=0.04; Open GWAS: OR=1.12, 95%CI=1.06-1.18, P=4.44×10-5, FDR-P=3.55×10-4), and Andro steroid monosulfate (FinnGen: OR=1.07, 95%CI=1.01-1.14, P=0.03, FDR-P=0.04; Open GWAS: OR=1.05, 95%CI=1.01-1.10, P=0.04, FDR-P=0.04) are positively associated with the risk of colorectal cancer (CRC). 1-oleoyl-2-docosahexaenoyl-GPC (FinnGen: OR=0.89, 95%CI=0.81-0.98, P=0.02, FDR-P=0.04; Open GWAS: OR=0.93, 95%CI=0.87-0.99, P=0.02, FDR-P=0.04) is negatively correlated with CRC risk.
Conclusions:
3 blood metabolites are associated with the risk of GC; 4 blood metabolites and metabolite ratios are associated with the risk of CRC.
Recently, studies investigating the connection between blood metabolites and gastrointestinal tumors have gained increased attention. A Mendelian randomization (MR) study is considered the second most persuasive research method to explore the causal relationship between exposure and outcome after RCT.
Material and methods:
This analysis utilized the inverse variance weighted (IVW) method, the weighted median (WM) method, and MR-Egger regression. Initially, we analyzed GWAS data from the FinnGen database to identify various metabolites and their ratios. Subsequently, we repeatedly analyzed GWAS data from the Open GWAS database to filter out duplicate results.
Results:
5-methyluridine [FinnGen : odds ratio (OR) =1.16, 95% confidence interval (CI) =1.02-1.31, P=0.03, FDR-P=0.04; Open GWAS: OR=1.08, 95%CI=1.01-1.17, P=0.03, FDR-P=0.04] and 1-dihomo-linolenylglycerol (FinnGen: OR=1.30, 95%CI=1.02-1.65, P=0.03, FDR-P=0.04; Open GWAS: OR=1.16, 95%CI=1.02-1.31, P=0.03, FDR-P=0.04) are positively associated with the risk of gastric cancer (GC). Sphingomyelin (FinnGen: OR=0.73, 95%CI=0.54-0.98, P=0.04, FDR-P=0.04; Open GWAS: OR=0.81, 95%CI=0.67-0.97, P=0.02, FDR-P=0.04) is negatively correlated with GC risk. Carnitine to propionylcarnitine (C3) ratio (FinnGen: OR=1.11, 95%CI=1.01-1.22, P=0.03, FDR-P=0.04; Open GWAS: OR=1.07, 95%CI=1.01-1.14, P=0.04, FDR-P=0.04), Arachidonate to linoleate ratio (FinnGen: OR=1.10, 95%CI=1.02-1.19, P=0.02, FDR-P=0.04; Open GWAS: OR=1.12, 95%CI=1.06-1.18, P=4.44×10-5, FDR-P=3.55×10-4), and Andro steroid monosulfate (FinnGen: OR=1.07, 95%CI=1.01-1.14, P=0.03, FDR-P=0.04; Open GWAS: OR=1.05, 95%CI=1.01-1.10, P=0.04, FDR-P=0.04) are positively associated with the risk of colorectal cancer (CRC). 1-oleoyl-2-docosahexaenoyl-GPC (FinnGen: OR=0.89, 95%CI=0.81-0.98, P=0.02, FDR-P=0.04; Open GWAS: OR=0.93, 95%CI=0.87-0.99, P=0.02, FDR-P=0.04) is negatively correlated with CRC risk.
Conclusions:
3 blood metabolites are associated with the risk of GC; 4 blood metabolites and metabolite ratios are associated with the risk of CRC.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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