Bayesian analysis of censored response data in family-based genetic association studies
File(s)Censored_data_BJ_26072016.pdf (342.88 KB)
Accepted version
Author(s)
Del Greco M, F
Pattaro, C
Minelli, C
Thompson, JR
Type
Journal Article
Abstract
Biomarkers are subject to censoring whenever some measurements are not quantifiable given a laboratory detection limit. Methods for handling censoring have received less attention in genetic epidemiology, and censored data are still often replaced with a fixed value. We compared different strategies for handling a left-censored continuous biomarker in a family-based study, where the biomarker is tested for association with a genetic variant, S, adjusting for a covariate, X. Allowing different correlations between X and S, we compared simple substitution of censored observations with the detection limit followed by a linear mixed effect model (LMM), Bayesian model with noninformative priors, Tobit model with robust standard errors, the multiple imputation (MI) with and without S in the imputation followed by a LMM. Our comparison was based on real and simulated data in which 20% and 40% censoring were artificially induced. The complete data were also analyzed with a LMM. In the MICROS study, the Bayesian model gave results closer to those obtained with the complete data. In the simulations, simple substitution was always the most biased method, the Tobit approach gave the least biased estimates at all censoring levels and correlation values, the Bayesian model and both MI approaches gave slightly biased estimates but smaller root mean square errors. On the basis of these results the Bayesian approach is highly recommended for candidate gene studies; however, the computationally simpler Tobit and the MI without S are both good options for genome-wide studies.
Date Issued
2016-05-24
Date Acceptance
2016-04-06
Citation
Biometrical Journal, 2016, 58 (5), pp.1039-1053
ISSN
1521-4036
Publisher
Wiley
Start Page
1039
End Page
1053
Journal / Book Title
Biometrical Journal
Volume
58
Issue
5
Copyright Statement
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the accepted version of the following article: Del Greco M., F., Pattaro, C., Minelli, C. and Thompson, J. R. (2016), Bayesian analysis of censored response data in family-based genetic association studies. Biom. J., which has been published in final form at http://dx.doi.org/10.1002/bimj.201400107.
Subjects
Bayesian methods
Genetic association studies
Left-censored data
Multiple imputation
Tobit model
Statistics & Probability
0104 Statistics
Publication Status
Published