Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/41551
Title: Comparison of variance estimators for meta-analysis of instrumental variable estimates
Authors: Schmidt, A. F.
Hingorani, A. D.
Jefferis, B. J.
White, J.
Groenwold, R.
Dudbridge, Frank
UCLEB Consortium
First Published: 2-Sep-2016
Publisher: Oxford University Press for International Epidemiological Association
Citation: International Journal of Epidemiology, 2016, 45 (6), pp. 1975-1986
Abstract: Background: Mendelian randomization studies perform instrumental variable (IV) analysis using genetic IVs. Results of individual Mendelian randomization studies can be pooled through meta-analysis. We explored how different variance estimators influence the meta-analysed IV estimate. Methods: Two versions of the delta method (IV before or after pooling), four bootstrap estimators, a jack-knife estimator and a heteroscedasticity-consistent (HC) variance estimator were compared using simulation. Two types of meta-analyses were compared, a two-stage meta-analysis pooling results, and a one-stage meta-analysis pooling datasets. Results: Using a two-stage meta-analysis, coverage of the point estimate using bootstrapped estimators deviated from nominal levels at weak instrument settings and/or outcome probabilities ≤ 0.10. The jack-knife estimator was the least biased resampling method, the HC estimator often failed at outcome probabilities ≤ 0.50 and overall the delta method estimators were the least biased. In the presence of between-study heterogeneity, the delta method before meta-analysis performed best. Using a one-stage meta-analysis all methods performed equally well and better than two-stage meta-analysis of greater or equal size. Conclusions: In the presence of between-study heterogeneity, two-stage meta-analyses should preferentially use the delta method before meta-analysis. Weak instrument bias can be reduced by performing a one-stage meta-analysis.
DOI Link: 10.1093/ije/dyw123
ISSN: 0300-5771
eISSN: 1464-3685
Links: https://academic.oup.com/ije/article/45/6/1975/2622845
http://hdl.handle.net/2381/41551
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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