论文标题
关于孟德尔随机化混合尺度治疗效果鲁棒鉴定(MR Misteri)和因果推断的估计
On Mendelian Randomization Mixed-Scale Treatment Effect Robust Identification (MR MiSTERI) and Estimation for Causal Inference
论文作者
论文摘要
如果定义仪器变量(IV)的遗传变异体被混淆和/或对未由治疗介导的感兴趣的结果具有水平的多效性效应,则标准的Mendelian随机分析可以产生偏见的结果。我们通过利用无效的IV,可以违反IV独立性和排除限制假设。提出的孟德尔随机混合尺度治疗效果鲁棒鉴定(Mr Misteri)方法依赖于(i)假设治疗效应在添加剂量表上与无效IV不同; (ii)由于混淆而引起的选择偏置在优势比量表上与无效的IV不同; (iii)结果的残余方差是异质的,因此随无效的IV而变化。我们正式确定它们的连接也可以鉴定出因静脉注射的无效静脉注射效果。在添加剂量表上存在多效应效应的普遍异质性的存在,其中迈斯特(Misteri)在这种环境中尤其有利,其中两种最近提出的强大估计方法MR GXE MR GXE和MR Genius可能会严重偏见。为了纳入多种,可能相关和弱的IV,MR研究中的一个常见挑战,我们开发了许多无效的工具(Mr Mawii Misteri)方法,以增强鉴定和提高的准确性Mawii Misteri被证明对水平的多效性,侵犯IV独立性假设和弱IIV IV偏见。仿真研究和实际数据分析结果都证明了拟议的M. Misteri方法的鲁棒性。
Standard Mendelian randomization analysis can produce biased results if the genetic variant defining the instrumental variable (IV) is confounded and/or has a horizontal pleiotropic effect on the outcome of interest not mediated by the treatment. We provide novel identification conditions for the causal effect of a treatment in presence of unmeasured confounding, by leveraging an invalid IV for which both the IV independence and exclusion restriction assumptions may be violated. The proposed Mendelian Randomization Mixed-Scale Treatment Effect Robust Identification (MR MiSTERI) approach relies on (i) an assumption that the treatment effect does not vary with the invalid IV on the additive scale; and (ii) that the selection bias due to confounding does not vary with the invalid IV on the odds ratio scale; and (iii) that the residual variance for the outcome is heteroscedastic and thus varies with the invalid IV. We formally establish that their conjunction can identify a causal effect even with an invalid IV subject to pleiotropy. MiSTERI is shown to be particularly advantageous in presence of pervasive heterogeneity of pleiotropic effects on additive scale, a setting in which two recently proposed robust estimation methods MR GxE and MR GENIUS can be severely biased. In order to incorporate multiple, possibly correlated and weak IVs, a common challenge in MR studies, we develop a MAny Weak Invalid Instruments (MR MaWII MiSTERI) approach for strengthened identification and improved accuracy MaWII MiSTERI is shown to be robust to horizontal pleiotropy, violation of IV independence assumption and weak IV bias. Both simulation studies and real data analysis results demonstrate the robustness of the proposed MR MiSTERI methods.