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Consistent Estimationin MendelianRandomization withSome InvalidInstruments Using aWeighted MedianEstimator Jack BowdenGeorge Davey SmithPhilip Haycock2016 год

Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
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Аннотация: ABSTRACT Developments in genome‐wide association studies and the increasing availability of summary genetic association data have made application of Mendelian randomization relatively straightforward. However, obtaining reliable results from a Mendelian randomization investigation remains problematic, as the conventional inverse‐variance weighted method only gives consistent estimates if all of the genetic variants in the analysis are valid instrumental variables. We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate. This estimator is consistent even when up to 50% of the information comes from invalid instrumental variables. In a simulation analysis, it is shown to have better finite‐sample Type 1 error rates than the inverse‐variance weighted method, and is complementary to the recently proposed MR‐Egger (Mendelian randomization‐Egger) regression method. In analyses of the causal effects of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol on coronary artery disease risk, the inverse‐variance weighted method suggests a causal effect of both lipid fractions, whereas the weighted median and MR‐Egger regression methods suggest a null effect of high‐density lipoprotein cholesterol that corresponds with the experimental evidence. Both median‐based and MR‐Egger regression methods should be considered as sensitivity analyses for Mendelian randomization investigations with multiple genetic variants.
Год издания: 2016
Авторы: Jack Bowden, George Davey Smith, Philip Haycock, Stephen Burgess
Издательство: Wiley
Источник: Genetic Epidemiology
Ключевые слова: Genetic Associations and Epidemiology, Genetic and phenotypic traits in livestock, Liver Disease Diagnosis and Treatment
Другие ссылки: Genetic Epidemiology (PDF)
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