BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon c...BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.展开更多
BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of pe...BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of peptic ulcers(PU).However,the precise causal relationship between these factors remains ambiguous.Consequently,this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.AIM To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein(VLDL)association with PU via genetic methods,guiding future clinical research.METHODS Genome-wide association study(GWAS)datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project(https://gwas.mrcieu.ac.uk).For the forward Mendelian randomization(MR)analysis,72 single nucleotide polymorphisms(SNPs)were identified as instrumental variables.These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL,with peptic ulcer as the outcome variable.Conversely,for the inverse MR analysis,no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome.All MR analyses utilized inverse variance weighted(IVW)as the primary analytical method.Additionally,weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects.Egger regression was used as a supplementary method to evaluate potential directional pleiotropy.Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.RESULTS The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer(IVW:OR=2.557,95%CI=1.274-5.132,P=0.008).However,no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.CONCLUSION In conclusion,our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers.However,further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.展开更多
基金Supported by the General Project of Medical and Health Technology Plan of Zhejiang Province,No.2020KY845.
文摘BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.
文摘BACKGROUND Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-lowdensity lipoprotein(VLDL)and the occurrence of peptic ulcers(PU).However,the precise causal relationship between these factors remains ambiguous.Consequently,this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer.AIM To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein(VLDL)association with PU via genetic methods,guiding future clinical research.METHODS Genome-wide association study(GWAS)datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project(https://gwas.mrcieu.ac.uk).For the forward Mendelian randomization(MR)analysis,72 single nucleotide polymorphisms(SNPs)were identified as instrumental variables.These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL,with peptic ulcer as the outcome variable.Conversely,for the inverse MR analysis,no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome.All MR analyses utilized inverse variance weighted(IVW)as the primary analytical method.Additionally,weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects.Egger regression was used as a supplementary method to evaluate potential directional pleiotropy.Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing.RESULTS The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer(IVW:OR=2.557,95%CI=1.274-5.132,P=0.008).However,no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis.CONCLUSION In conclusion,our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers.However,further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.
