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The UK BiLEVE and Mendelian randomisation: using multivariable instrumental variables to address "damned if you, damned if you don't" adjustment problems.

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Woolf, Benjamin 
Gill, Dipender 
Sallis, Hannah 
Munafò, Marcus R 

Abstract

OBJECTIVE: To explore the use of multivariable instrumental variables to resolve the "damned if you do, damned if you don't" adjustment problem created for Mendelian randomisation (MR) analysis using the smoking or lung function related phenotypes in the UK Biobank (UKB). RESULT: "damned if you do, damned if you don't" adjustment problems occur when both adjusting and not-adjusting for a variable will induce bias in an analysis. One instance of this occurs because the genotyping chip of UKB participants differed based on lung function/smoking status. In simulations, we show that multivariable instrumental variables analyses can attenuate potential collider bias introduced by adjusting for a proposed covariate, such as the UKB genotyping chip. We then explore the effect of adjusting for genotyping chip in a multivariable MR model exploring the effect of smoking on seven medical outcomes (lung cancer, emphysema, hypertension, stroke, heart diseases, depression, and disabilities). We additionally compare our results to a traditional univariate MR analysis using genome-wide analyses summary statistics which had and had not adjusted for genotyping chip. This analysis implies that the difference in genotyping chip has introduced only a small amount of bias.

Description

Keywords

Humans, Genome-Wide Association Study, Smoking, Heart Diseases, Pulmonary Emphysema, United Kingdom

Journal Title

BMC Res Notes

Conference Name

Journal ISSN

1756-0500
1756-0500

Volume Title

16

Publisher

Springer Science and Business Media LLC
Sponsorship
Economic and Social Research Council (ES/P000630/1)