RT Journal Article
T1 Avoiding collider bias in Mendelian randomization when performing  stratified analyses
A1 Coscia, Claudia
A1 Gill, Dipender
A1 Benítez, Raquel
A1 Pérez Pérez, Teresa
A1 Malats, Nuria
A1 Burgess, Stephen
A2 Hofman, Albert
AB Mendelian randomization (MR) uses genetic variants as instrumental variables to investigate the causal effect of a risk factor on an outcome. A collider is a variable influenced by two or more other variables. Naive calculation of MR estimates in strata of the population defined by a collider, such as a variable affected by the risk factor, can result in collider bias. We propose an approach that allows MR estimation in strata of the population while avoiding collider bias. This approach constructs a new variable, the residual collider, as the residual from regression of the collider on the genetic instrument, and then calculates causal estimates in strata defined by quantiles of the residual collider. Estimates stratified on the residual collider will typically have an equivalent interpretation to estimates stratified on the collider, but they are not subject to collider bias. We apply the approach in several simulation scenarios considering different characteristics of the collider variable and strengths of the instrument. We then apply the proposed approach to investigate the causal effect of smoking on bladder cancer in strata of the population defined by bodyweight. The new approach generated unbiased estimates in all the simulation settings. In the applied example, we observed a trend in the stratum-specific MR estimates at different bodyweight levels that suggested stronger effects of smoking on bladder cancer among individuals with lower bodyweight. The proposed approach can be used to perform MR studying heterogeneity among subgroups of the population while avoiding collider bias.
PB Springer
SN 0393-2990
YR 2022
FD 2022-05-31
LK https://hdl.handle.net/20.500.14352/111057
UL https://hdl.handle.net/20.500.14352/111057
LA eng
NO Coscia C, Gill D, Benítez R, Pérez T, Malats N, Burgess S. Avoiding collider bias in Mendelian randomization when performing stratified analyses. Eur J Epidemiol. 2022;37(7):671-682. doi:10.1007/s10654-022-00879-0
NO Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society
NO United Kingdom Research and Innovation Medical Research Council
NO National Institute for Health Research Cambridge Biomedical Research Centre
NO Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain
NO Ministerio de Ciencia e Innovación, Spain
NO CIBERONC, Insitituto de Salud Carlos III, Spain
NO British Heart Foundation Centre of Research Excellence, Imperial College
NO National Institute for Health Research Clinical Lectureship, St George's, University of London.
DS Docta Complutense
RD 18 jun 2025