Modal-based estimation via heterogeneity-penalized weighting: model averaging for consistent and efficient estimation in Mendelian randomization when a plurality of candidate instruments are valid.

International Journal of Epidemiology
Stephen BurgessChristopher N Foley

Abstract

A robust method for Mendelian randomization does not require all genetic variants to be valid instruments to give consistent estimates of a causal parameter. Several such methods have been developed, including a mode-based estimation method giving consistent estimates if a plurality of genetic variants are valid instruments; i.e. there is no larger subset of invalid instruments estimating the same causal parameter than the subset of valid instruments. We here develop a model-averaging method that gives consistent estimates under the same 'plurality of valid instruments' assumption. The method considers a mixture distribution of estimates derived from each subset of genetic variants. The estimates are weighted such that subsets with more genetic variants receive more weight, unless variants in the subset have heterogeneous causal estimates, in which case that subset is severely down-weighted. The mode of this mixture distribution is the causal estimate. This heterogeneity-penalized model-averaging method has several technical advantages over the previously proposed mode-based estimation method. The heterogeneity-penalized model-averaging method outperformed the mode-based estimation in terms of efficiency and outperformed other ...Continue Reading

References

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Aug 24, 2007·Statistical Methods in Medical Research·Vanessa Didelez, Nuala Sheehan
Feb 18, 2011·BMJ : British Medical Journal·UNKNOWN C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC)John Danesh
Mar 19, 2011·International Journal of Epidemiology·Stephen BurgessUNKNOWN CRP CHD Genetics Collaboration
Mar 25, 2011·Statistics in Medicine·Stephen Burgess, Simon G Thompson
Jun 5, 2013·Statistics in Medicine·Stephen Burgess, UNKNOWN CRP CHD Genetics Collaboration
Jul 19, 2013·American Journal of Epidemiology·Brandon L Pierce, Stephen Burgess
Oct 8, 2013·Nature Genetics·Cristen J WillerUNKNOWN Global Lipids Genetics Consortium
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Mar 17, 2015·European Journal of Epidemiology·Stephen BurgessUNKNOWN EPIC- InterAct Consortium
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Oct 19, 2017·International Journal of Epidemiology·Fernando Pires HartwigJack Bowden

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Citations

Apr 7, 2020·Genetic Epidemiology·Eric A W Slob, Stephen Burgess
Aug 11, 2020·Wellcome Open Research·Stephen BurgessEvropi Theodoratou
Oct 26, 2018·Stroke; a Journal of Cerebral Circulation·Susanna C LarssonUNKNOWN MEGASTROKE Project of the International Stroke Genetics Consortium
Jan 19, 2020·Nature Communications·Stephen BurgessJoanna M M Howson
Apr 2, 2020·Cold Spring Harbor Perspectives in Medicine·Frank Dudbridge
Oct 16, 2018·Bone·Susanna C LarssonStephen Burgess
Jun 23, 2021·Statistics in Medicine·Apostolos GkatzionisPaul J Newcombe
Jul 25, 2021·Nature Reviews. Genetics·William R Reay, Murray J Cairns
Jan 28, 2022·European Journal of Human Genetics : EJHG·Christiaan de LeeuwDanielle Posthuma

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