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弱工具变量下的多变量孟德尔随机化：贝叶斯与频率学派方法比较AI 解读

Weak instruments are a well known limitation for valid causal inference in Mendelian randomization studies. In the single exposure setting, weak instrument bias can be mitigated by selecting genetic instruments which are strongly associated with the exposure according to p-value and/or F-statistic thresholds. However, in the multi-exposure setting, genetic instruments may be strongly associated with an exposure but weakly associated with it conditional on all other exposures…

遗传工具变量下边际处理效应的有效半参数估计AI 解读

Alcohol misuse is a key target of public health strategies aimed at reducing cardiovascular risk. The effect of excessive alcohol consumption on blood pressure may vary systematically with individuals' unobserved propensity to engage in heavy drinking, complicating causal inference with observational data. The marginal treatment effects framework uses an instrumental variable for treatment choice (excessive alcohol consumption) to study how selection into treatment is linked…

基于分层的非线性效应工具变量分析框架AI 解读

Nonlinear causal effects are prevalent in many research scenarios involving continuous exposures, and instrumental variables (IVs) can be employed to investigate such effects, particularly in the presence of unmeasured confounders. However, common IV methods for nonlinear effect analysis, such as IV regression or the control-function method, have inherent limitations, leading to either low statistical power or potentially misleading conclusions. In this work, we propose an…

孟德尔随机化中的异常工具变量检测AI 解读

Mendelian Randomisation (MR) uses genetic variants as instrumental variables to infer causal effects of exposures on an outcome. One key assumption of MR is that the genetic variants used as instrumental variables are independent of the outcome conditional on the risk factor and unobserved confounders. Violations of this assumption, i.e. the effect of the instrumental variables on the outcome through a path other than the risk factor included in the model (which can be…

通过连续时间建模估计孟德尔随机化中的时变暴露效应AI 解读

Mendelian randomization is an instrumental variable method that utilizes genetic information to investigate the causal effect of a modifiable exposure on an outcome. In most cases, the exposure changes over time. Understanding the time-varying causal effect of the exposure can yield detailed insights into mechanistic effects and the potential impact of public health interventions. Recently, a growing number of Mendelian randomization studies have attempted to explore…

选择相关遗传变异后的比例共定位频率学检验AI 解读

Colocalization analyses assess whether two traits are affected by the same or distinct causal genetic variants in a single gene region. A class of Bayesian colocalization tests are now routinely used in practice; for example, for genetic analyses in drug development pipelines. In this work, we consider an alternative frequentist approach to colocalization testing that examines the proportionality of genetic associations with each trait. The proportional colocalization…

选择无效工具变量以改进双样本汇总数据的孟德尔随机化AI 解读

Mendelian randomization (MR) is a widely-used method to estimate the causal relationship between a risk factor and disease. A fundamental part of any MR analysis is to choose appropriate genetic variants as instrumental variables. Genome-wide association studies often reveal that hundreds of genetic variants may be robustly associated with a risk factor, but in some situations investigators may have greater confidence in the instrument validity of only a smaller subset of…

暴露测量误差导致的多变量孟德尔随机化偏倚AI 解读

Multivariable Mendelian randomization estimates the causal effect of multiple exposures on an outcome, typically using summary statistics of genetic variant associations. However, exposures of interest in Mendelian randomization applications will often be measured with error. The summary statistics will therefore not be of the genetic associations with the exposure, but with the exposure measured with error. Classical measurement error will not bias genetic association…

利用多变量孟德尔随机化分离共享聚集遗传预测因子的性状效应AI 解读

When genetic variants in a gene cluster are associated with a disease outcome, the causal pathway from the variants to the outcome can be difficult to disentangle. For example, the chemokine receptor gene cluster contains genetic variants associated with various cytokines. Associations between variants in this cluster and stroke risk may be driven by any of these cytokines. Multivariable Mendelian randomization is an extension of standard univariable Mendelian randomization…