PDF(Pubmed)
Abstract：
UNASSIGNED: Liver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer\'s disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study.
UNASSIGNED: Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer\'s disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses.
UNASSIGNED: Multivariable MR analysis showed causal association between Alzheimer\'s disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer\'s disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer\'s disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer\'s disease, and LIHC susceptibility.
UNASSIGNED: A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer\'s disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.
UNASSIGNED: Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer\'s disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses.
UNASSIGNED: Multivariable MR analysis showed causal association between Alzheimer\'s disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer\'s disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer\'s disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer\'s disease, and LIHC susceptibility.
UNASSIGNED: A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer\'s disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.
摘要：
■肝肝细胞癌（LIHC）表现出多因素病因，阴险的发作，和显著较低的5年生存率。我们旨在评估暴露因素的因果影响(阿尔茨海默病，血小板计数,双巧，每天吸烟，酒精消费,和心内膜炎）使用双样本孟德尔随机（MR）研究来评估LIHC的风险。
■与阿尔茨海默病密切相关的独立单核苷酸多态性（SNPs），血小板计数,双巧，每日香烟消费，酒精摄入量,从相应的全基因组关联研究(GWAS)中选择心内膜炎作为工具变量(IVs).LIHC的遗传汇总统计数据来自GWAS，其中包括168例病例和372,016个欧洲个体对照。进行了多变量MR分析，以发现6个暴露因素与LIHC风险之间的因果关系。采用逆方差加权(IVW)-MR作为主要分析，和MR-Egger回归，LASSO回归,和加权中位数方法作为补充分析。
■多变量MR分析显示阿尔茨海默病[赔率（OR）=0.9999，95％置信区间（CI）=0.9998-0.9999，p=0.0010]，血小板计数（OR=0.9997，95%CI=0.9995-0.9999，p=0.0066），饮酒（OR=0.9994，95%CI=0.9990-0.9999，p=0.0098）和LIHC结果。IVW-MR之后,MR-Egger和LASSO测试,结果仍然很显著。接下来,我们使用不同的MR方法分析血小板计数，酒精消费,和阿尔茨海默病分开。此外，漏斗图和MR-Egger截距都提供了令人信服的证据来反驳在血小板计数之间的相关性中存在方向性多效性,酒精消费,阿尔茨海默病和LIHC的风险。IVW-MR分析显示血小板计数升高与LIHC风险降低之间存在显著的因果关系(OR=0.9996,95%CI=0.9995-0.9998,p=0.0005)。同样，加权中位数分析显示血小板计数与LIHC风险呈负相关(OR=0.9995,95%CI=0.9993-0.9999;p=0.0160).相反，我们观察到饮酒对LIHC发生率的正因果效应(OR=1.0004,95%CI=0.9999-1.0009).然而,酒精假设之间没有发现显著的因果关系，老年痴呆症,和LIHC敏感性。
■血小板计数之间存在显著的因果关系，酒精消费,老年痴呆症,和LIHC的风险增加。该研究提供了令人信服的证据，表明基于血小板计数的基因预测对LIHC的易感性降低。研究表明，血小板计数升高可能是对抗LIHC的保护机制。这些发现可能为LIHC预防提供临床策略。
■与阿尔茨海默病密切相关的独立单核苷酸多态性（SNPs），血小板计数,双巧，每日香烟消费，酒精摄入量,从相应的全基因组关联研究(GWAS)中选择心内膜炎作为工具变量(IVs).LIHC的遗传汇总统计数据来自GWAS，其中包括168例病例和372,016个欧洲个体对照。进行了多变量MR分析，以发现6个暴露因素与LIHC风险之间的因果关系。采用逆方差加权(IVW)-MR作为主要分析，和MR-Egger回归，LASSO回归,和加权中位数方法作为补充分析。
■多变量MR分析显示阿尔茨海默病[赔率（OR）=0.9999，95％置信区间（CI）=0.9998-0.9999，p=0.0010]，血小板计数（OR=0.9997，95%CI=0.9995-0.9999，p=0.0066），饮酒（OR=0.9994，95%CI=0.9990-0.9999，p=0.0098）和LIHC结果。IVW-MR之后,MR-Egger和LASSO测试,结果仍然很显著。接下来,我们使用不同的MR方法分析血小板计数，酒精消费,和阿尔茨海默病分开。此外，漏斗图和MR-Egger截距都提供了令人信服的证据来反驳在血小板计数之间的相关性中存在方向性多效性,酒精消费,阿尔茨海默病和LIHC的风险。IVW-MR分析显示血小板计数升高与LIHC风险降低之间存在显著的因果关系(OR=0.9996,95%CI=0.9995-0.9998,p=0.0005)。同样，加权中位数分析显示血小板计数与LIHC风险呈负相关(OR=0.9995,95%CI=0.9993-0.9999;p=0.0160).相反，我们观察到饮酒对LIHC发生率的正因果效应(OR=1.0004,95%CI=0.9999-1.0009).然而,酒精假设之间没有发现显著的因果关系，老年痴呆症,和LIHC敏感性。
■血小板计数之间存在显著的因果关系，酒精消费,老年痴呆症,和LIHC的风险增加。该研究提供了令人信服的证据，表明基于血小板计数的基因预测对LIHC的易感性降低。研究表明，血小板计数升高可能是对抗LIHC的保护机制。这些发现可能为LIHC预防提供临床策略。
