PDF(Pubmed)
Abstract：
BACKGROUND: Previous research has underscored the correlation between Alzheimer\'s disease (AD) and erectile dysfunction (ED). However, due to inherent limitations of observational studies, the causative relationship remains inconclusive.
METHODS: Utilizing publicly available data from genome-wide association studies (GWAS) summary statistics, this study probed the potential causal association between AD and ED using univariate Mendelian randomization (MR). Further, the multivariable MR assessed the confounding effects of six cardiovascular diseases (CVDs). The primary approach employed was inverse variance weighted (IVW), supplemented by three additional methods. A series of sensitivity analyses were conducted to ensure the robustness of the results.
RESULTS: In the forward MR analysis, the IVW method revealed causal evidence of genetically predicted AD being a risk factor for ED (OR = 1.077, 95% CI 1.007∼1.152, P = 0.031). Reverse analysis did not demonstrate any causal evidence linking ED to AD (OR = 1.018, 95% CI 0.974∼1.063, P = 0.430). Multivariable MR analysis showed that after adjusting for coronary heart disease (OR = 1.082, 95% CI 0.009∼1.160, P = 0.027), myocardial infarction (OR = 1.085, 95% CI 1.012∼1.163, P = 0.022), atrial fibrillation (OR = 1.076, 95% CI 1.002∼1.154, P = 0.043), heart failure (OR = 1.103, 95% CI 1.024∼1.188, P = 0.010), ischemic stroke (OR = 1.079, 95% CI 1.009∼1.154, P = 0.027), hypertension (OR = 1.092, 95% CI 1.011∼1.180, P = 0.025), and all models (OR = 1.115, 95% CI 1.024∼1.214, P = 0.012), the causal association between AD and ED persisted. Sensitivity analyses confirmed the absence of pleiotropy, heterogeneity, and outliers, validating the robustness of our results (P > 0.05).
CONCLUSIONS: This MR study consistently evidences a causal effect of genetically predicted AD on the risk of ED, independent of certain CVDs, yet offers no evidence for a reverse effect from ED.
METHODS: Utilizing publicly available data from genome-wide association studies (GWAS) summary statistics, this study probed the potential causal association between AD and ED using univariate Mendelian randomization (MR). Further, the multivariable MR assessed the confounding effects of six cardiovascular diseases (CVDs). The primary approach employed was inverse variance weighted (IVW), supplemented by three additional methods. A series of sensitivity analyses were conducted to ensure the robustness of the results.
RESULTS: In the forward MR analysis, the IVW method revealed causal evidence of genetically predicted AD being a risk factor for ED (OR = 1.077, 95% CI 1.007∼1.152, P = 0.031). Reverse analysis did not demonstrate any causal evidence linking ED to AD (OR = 1.018, 95% CI 0.974∼1.063, P = 0.430). Multivariable MR analysis showed that after adjusting for coronary heart disease (OR = 1.082, 95% CI 0.009∼1.160, P = 0.027), myocardial infarction (OR = 1.085, 95% CI 1.012∼1.163, P = 0.022), atrial fibrillation (OR = 1.076, 95% CI 1.002∼1.154, P = 0.043), heart failure (OR = 1.103, 95% CI 1.024∼1.188, P = 0.010), ischemic stroke (OR = 1.079, 95% CI 1.009∼1.154, P = 0.027), hypertension (OR = 1.092, 95% CI 1.011∼1.180, P = 0.025), and all models (OR = 1.115, 95% CI 1.024∼1.214, P = 0.012), the causal association between AD and ED persisted. Sensitivity analyses confirmed the absence of pleiotropy, heterogeneity, and outliers, validating the robustness of our results (P > 0.05).
CONCLUSIONS: This MR study consistently evidences a causal effect of genetically predicted AD on the risk of ED, independent of certain CVDs, yet offers no evidence for a reverse effect from ED.
摘要：
背景：先前的研究强调了阿尔茨海默病（AD）与勃起功能障碍（ED）之间的相关性。然而,由于观察性研究的固有局限性，因果关系仍然没有定论。
方法：利用来自全基因组关联研究（GWAS）汇总统计的公开数据，本研究使用单变量孟德尔随机化(MR)探讨了AD和ED之间的潜在因果关系.Further,多变量MR评估了6种心血管疾病(CVDs)的混杂效应.采用的主要方法是方差逆加权(IVW)，补充三种方法。进行了一系列敏感性分析，以确保结果的稳健性。
结果：在正向MR分析中，IVW方法揭示了遗传预测的AD是ED的危险因素的因果证据（OR=1.077，95％CI1.007～1.152，P=0.031）。反向分析未证明ED与AD之间存在因果关系(OR=1.018,95%CI0.974～1.063,P=0.430)。多变量MR分析显示,校正冠心病后(OR=1.082,95%CI0.009~1.160,P=0.027),心肌梗死(OR=1.085,95%CI1.012~1.163,P=0.022),心房颤动(OR=1.076，95%CI1.002~1.154，P=0.043)，心力衰竭(OR=1.103，95%CI1.024~1.188，P=0.010)，缺血性卒中(OR=1.079，95%CI1.009~1.154，P=0.027)，高血压(OR=1.092，95%CI1.011~1.180，P=0.025)，和所有模型(OR=1.115，95%CI1.024~1.214，P=0.012)，AD和ED之间的因果关系仍然存在.敏感性分析证实了多效性的缺失，异质性，和异常值，验证了我们结果的稳健性(P>0.05)。
结论：这项MR研究一致证明了遗传预测的AD对ED风险的因果影响，独立于某些CVD，但没有证据表明ED有相反的作用。
方法：利用来自全基因组关联研究（GWAS）汇总统计的公开数据，本研究使用单变量孟德尔随机化(MR)探讨了AD和ED之间的潜在因果关系.Further,多变量MR评估了6种心血管疾病(CVDs)的混杂效应.采用的主要方法是方差逆加权(IVW)，补充三种方法。进行了一系列敏感性分析，以确保结果的稳健性。
结果：在正向MR分析中，IVW方法揭示了遗传预测的AD是ED的危险因素的因果证据（OR=1.077，95％CI1.007～1.152，P=0.031）。反向分析未证明ED与AD之间存在因果关系(OR=1.018,95%CI0.974～1.063,P=0.430)。多变量MR分析显示,校正冠心病后(OR=1.082,95%CI0.009~1.160,P=0.027),心肌梗死(OR=1.085,95%CI1.012~1.163,P=0.022),心房颤动(OR=1.076，95%CI1.002~1.154，P=0.043)，心力衰竭(OR=1.103，95%CI1.024~1.188，P=0.010)，缺血性卒中(OR=1.079，95%CI1.009~1.154，P=0.027)，高血压(OR=1.092，95%CI1.011~1.180，P=0.025)，和所有模型(OR=1.115，95%CI1.024~1.214，P=0.012)，AD和ED之间的因果关系仍然存在.敏感性分析证实了多效性的缺失，异质性，和异常值，验证了我们结果的稳健性(P>0.05)。
结论：这项MR研究一致证明了遗传预测的AD对ED风险的因果影响，独立于某些CVD，但没有证据表明ED有相反的作用。
