Debiased inverse-variance weighted estimator in two-sample summary-data Mendelian randomization
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Publication:2054477
DOI10.1214/20-AOS2027zbMATH Open1486.62292arXiv1911.09802OpenAlexW3203511452MaRDI QIDQ2054477FDOQ2054477
Authors: Ting Ye, Jun Shao, Hyunseung Kang 
Publication date: 3 December 2021
Published in: The Annals of Statistics (Search for Journal in Brave)
Abstract: Mendelian randomization (MR) has become a popular approach to study the effect of a modifiable exposure on an outcome by using genetic variants as instrumental variables. A challenge in MR is that each genetic variant explains a relatively small proportion of variance in the exposure and there are many such variants, a setting known as many weak instruments. To this end, we provide a theoretical characterization of the statistical properties of two popular estimators in MR, the inverse-variance weighted (IVW) estimator and the IVW estimator with screened instruments using an independent selection dataset, under many weak instruments. We then propose a debiased IVW estimator, a simple modification of the IVW estimator, that is robust to many weak instruments and doesn't require screening. Additionally, we present two instrument selection methods to improve the efficiency of the new estimator when a selection dataset is available. An extension of the debiased IVW estimator to handle balanced horizontal pleiotropy is also discussed. We conclude by demonstrating our results in simulated and real datasets.
Full work available at URL: https://arxiv.org/abs/1911.09802
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Cites Work
- Instrumental Variables Regression with Weak Instruments
- Consistent Estimation with a Large Number of Weak Instruments
- Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score
- Mendelian randomization as an instrumental variable approach to causal inference
Cited In (9)
- Conditional inference in \textit{cis}-Mendelian randomization using weak genetic factors
- Breaking the winner's curse in Mendelian randomization: rerandomized inverse variance weighted estimator
- Weak‐instrument robust tests in two‐sample summary‐data Mendelian randomization
- Mendelian Randomization Mixed-Scale Treatment Effect Robust Identification and Estimation for Causal Inference
- Instrumental variable model average with applications in Mendelian randomization
- A Novel Penalized Inverse-Variance Weighted Estimator for Mendelian Randomization with Applications to COVID-19 Outcomes
- Using multiple genetic variants as instrumental variables for modifiable risk factors
- Approximation of bias and mean‐squared error in two‐sample Mendelian randomization analyses
- Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score
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