PDF(Pubmed)
Abstract：
UNASSIGNED: Evidence has been increasingly pointing towards a potential link between phenotypes related to obesity and the incidence of colorectal cancer. However, confirming this as a direct causal connection remains elusive. This investigation aims to elucidate the causative links between obesity-associated phenotypes and the incidence of colorectal cancer.
UNASSIGNED: Employing the Two Sample Mendelian Randomization (TwoSampleMR) R package, analyses were conducted using Mendelian randomization (MR) to discern potential causative links between obesity categories sourced from both the Institute for Education and University (IEU) Open GWAS Project and Zenodo, and colorectal tumors (data obtained from IEU Open GWAS and FinnGen). For primary evaluations, the study utilized the Wald ratio and the Inverse Variance Weighting (IVW) methods, while the MR-Egger approach was integrated for sensitivity assessment. Bidirectional Mendelian Randomization (Bidirectional MR), as well as Linkage Disequilibrium (LD) Score Regression with well-imputed HapMap3 single nucleotide polymorphisms (SNPs), were additionally executed. Sensitivity assessments entailed IVW, MR-Egger methodologies to assess heterogeneity and pleiotropy, along with a leave-one-out strategy. Instrumental variables were chosen judiciously based on predetermined P-value thresholds and F-statistics.
UNASSIGNED: Results from MR evaluations did not identify a clear causative link between BMI and colorectal malignancy. Conversely, both measures of obesity, the Waist-Hip Ratio (WHR) and its adjusted form for BMI (WHRadjBMI), displayed a connection to increased risk of colorectal cancer, especially prominent among female subjects. Reverse MR analyses dismissed potential reverse causality between colorectal malignancies and obesity. A significant genetic interplay was observed between WHR, WHRadjBMI, and colorectal cancer instances. Ensuing MR probes spotlighted inflammatory bowel ailment as a protective factor, while salad intake was indicated as a potential risk concerning colorectal malignancies. Sensitivity reviews, which included tests for both pleiotropy and heterogeneity, validated the robustness of the MR findings.
UNASSIGNED: Findings from this research indicate that specific obesity-related parameters, notably WHR and WHRadjBMI, carry a causal relationship with an elevated colorectal cancer risk. The impact is distinctly more evident among females. Such insights might be pivotal for public health deliberations, hinting that individuals boasting a high WHR might necessitate intensified colorectal cancer screenings.
UNASSIGNED: Employing the Two Sample Mendelian Randomization (TwoSampleMR) R package, analyses were conducted using Mendelian randomization (MR) to discern potential causative links between obesity categories sourced from both the Institute for Education and University (IEU) Open GWAS Project and Zenodo, and colorectal tumors (data obtained from IEU Open GWAS and FinnGen). For primary evaluations, the study utilized the Wald ratio and the Inverse Variance Weighting (IVW) methods, while the MR-Egger approach was integrated for sensitivity assessment. Bidirectional Mendelian Randomization (Bidirectional MR), as well as Linkage Disequilibrium (LD) Score Regression with well-imputed HapMap3 single nucleotide polymorphisms (SNPs), were additionally executed. Sensitivity assessments entailed IVW, MR-Egger methodologies to assess heterogeneity and pleiotropy, along with a leave-one-out strategy. Instrumental variables were chosen judiciously based on predetermined P-value thresholds and F-statistics.
UNASSIGNED: Results from MR evaluations did not identify a clear causative link between BMI and colorectal malignancy. Conversely, both measures of obesity, the Waist-Hip Ratio (WHR) and its adjusted form for BMI (WHRadjBMI), displayed a connection to increased risk of colorectal cancer, especially prominent among female subjects. Reverse MR analyses dismissed potential reverse causality between colorectal malignancies and obesity. A significant genetic interplay was observed between WHR, WHRadjBMI, and colorectal cancer instances. Ensuing MR probes spotlighted inflammatory bowel ailment as a protective factor, while salad intake was indicated as a potential risk concerning colorectal malignancies. Sensitivity reviews, which included tests for both pleiotropy and heterogeneity, validated the robustness of the MR findings.
UNASSIGNED: Findings from this research indicate that specific obesity-related parameters, notably WHR and WHRadjBMI, carry a causal relationship with an elevated colorectal cancer risk. The impact is distinctly more evident among females. Such insights might be pivotal for public health deliberations, hinting that individuals boasting a high WHR might necessitate intensified colorectal cancer screenings.
摘要：
■越来越多的证据表明与肥胖相关的表型与结直肠癌发病率之间存在潜在的联系。然而,确认这是一个直接的因果关系仍然难以捉摸。这项研究旨在阐明肥胖相关表型与结直肠癌发病率之间的因果关系。
■采用双样本孟德尔随机化（TwoSampleMR）R包，使用孟德尔随机化（MR）进行分析，以辨别来自教育和大学研究所（IEU）开放GWAS项目和Zenodo的肥胖类别之间的潜在因果关系，和结肠直肠肿瘤（数据来自IEUOpenGWAS和FinnGen）。对于主要评估，这项研究利用了沃尔德比率和逆方差加权(IVW)方法，而MR-Egger方法用于敏感性评估。双向孟德尔随机化（双向MR），以及具有良好估算的HapMap3单核苷酸多态性（SNP）的连锁不平衡（LD）得分回归，被额外执行。敏感性评估需要IVW，评估异质性和多效性的MR-Egger方法，还有一个离开的策略。基于预定的P值阈值和F统计量明智地选择仪器变量。
■MR评估结果未确定BMI与结直肠恶性肿瘤之间的明确因果关系。相反，这两种肥胖指标，腰臀比(WHR)及其BMI的调整形式(WHRadjBMI)，显示出与结直肠癌风险增加有关，在女性受试者中尤其突出。反向MR分析排除了结直肠恶性肿瘤和肥胖之间的潜在反向因果关系。在WHR之间观察到了显著的遗传相互作用，WHRadjBMI,和结肠直肠癌的例子。随后的MR探针突出了炎症性肠病作为保护因素，而沙拉摄入被认为是结直肠恶性肿瘤的潜在风险。敏感性审查，其中包括多效性和异质性的测试，验证了MR检查结果的稳健性。
■这项研究的结果表明，与肥胖相关的具体参数，特别是WHR和WHRadjBMI，与结直肠癌风险升高有因果关系。这种影响在女性中明显更为明显。这些见解可能对公共卫生审议至关重要，暗示拥有高WHR的个体可能需要加强结直肠癌筛查。
■采用双样本孟德尔随机化（TwoSampleMR）R包，使用孟德尔随机化（MR）进行分析，以辨别来自教育和大学研究所（IEU）开放GWAS项目和Zenodo的肥胖类别之间的潜在因果关系，和结肠直肠肿瘤（数据来自IEUOpenGWAS和FinnGen）。对于主要评估，这项研究利用了沃尔德比率和逆方差加权(IVW)方法，而MR-Egger方法用于敏感性评估。双向孟德尔随机化（双向MR），以及具有良好估算的HapMap3单核苷酸多态性（SNP）的连锁不平衡（LD）得分回归，被额外执行。敏感性评估需要IVW，评估异质性和多效性的MR-Egger方法，还有一个离开的策略。基于预定的P值阈值和F统计量明智地选择仪器变量。
■MR评估结果未确定BMI与结直肠恶性肿瘤之间的明确因果关系。相反，这两种肥胖指标，腰臀比(WHR)及其BMI的调整形式(WHRadjBMI)，显示出与结直肠癌风险增加有关，在女性受试者中尤其突出。反向MR分析排除了结直肠恶性肿瘤和肥胖之间的潜在反向因果关系。在WHR之间观察到了显著的遗传相互作用，WHRadjBMI,和结肠直肠癌的例子。随后的MR探针突出了炎症性肠病作为保护因素，而沙拉摄入被认为是结直肠恶性肿瘤的潜在风险。敏感性审查，其中包括多效性和异质性的测试，验证了MR检查结果的稳健性。
■这项研究的结果表明，与肥胖相关的具体参数，特别是WHR和WHRadjBMI，与结直肠癌风险升高有因果关系。这种影响在女性中明显更为明显。这些见解可能对公共卫生审议至关重要，暗示拥有高WHR的个体可能需要加强结直肠癌筛查。
