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Title: Bayesian analysis of censored response data in family-based genetic association studies
Authors: Del Greco M, Fabiola
Pattaro, Cristian
Minelli, Cosetta
Thompson, John R.
First Published: 24-May-2016
Publisher: Wiley-VCH Verlag for 1.Deutsche Region der Internationalen Biometrischen Gesellschaft (IBS-DR) 2.Region Österreich-Schweiz (ROeS) der Internationalen Biometrischen Gesellschaft (IBS)
Citation: Biometrical Journal, 2016, 58 (5), pp. 1039-1053
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.
DOI Link: 10.1002/bimj.201400107
ISSN: 0323-3847
eISSN: 1521-4036
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2016, Wiley-VCH Verlag.
Description: The file associated with this record is under permanent embargo at the request of the publisher. The article may be available from the links above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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