Impact of selection bias on estimation of subsequent event risk

Authors

Yi-Juan Hu, Emory University, Atlanta
Amand F. Schmidt, Emory University, USA.
Frank Dudbridge, Emory University, USA.
Michael V. Holmes, Emory University, USA.
James M. Brophy, Emory University, USA.
Vinicius Tragante, Emory University, USA.
Ziyi Li, Emory University, USA.
Peizhou Liao, Emory University, USA.
Arshed A. Quyyumi, Emory University, USA.
The GENIUS-CHD Consortium
Salim S. Virani, Michael E. DeBakey Veterans Affairs Hospital, USA.Follow

Document Type

Article

Department

Cardiology; Office of the Provost

Abstract

Background: Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown.
Methods and results: We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was Conclusions: In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal.

Comments

Pagination is not provided by the author/publisher. This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Circulation: Cardiovascular Genetics

DOI

10.1161/CIRCGENETICS.116.001616

Recommended Citation

Hu, Y., Schmidt, A. F., Dudbridge, F., Holmes, M. V., Brophy, J. M., Tragante, V., Li, Z., Liao, P., Quyyumi, A. A., The GENIUS-CHD Consortium, ., Virani, S. S. (2017). Impact of selection bias on estimation of subsequent event risk. Circulation: Cardiovascular Genetics, 10(5), e001616.
Available at: https://ecommons.aku.edu/provost_office/680