Bayesian methods to overcome the winner's curse in genetic studies

DOI10.1214/10-AOAS373zbMATH Open1220.62027arXiv0907.2770OpenAlexW3104135133MaRDI QIDQ542467FDOQ542467

Authors: Lizhen Xu, Radu V. Craiu, Lei Sun 

Publication date: 10 June 2011

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Parameter estimates for associated genetic variants, report ed in the initial discovery samples, are often grossly inflated compared to the values observed in the follow-up replication samples. This type of bias is a consequence of the sequential procedure in which the estimated effect of an associated genetic marker must first pass a stringent significance threshold. We propose a hierarchical Bayes method in which a spike-and-slab prior is used to account for the possibility that the significant test result may be due to chance. We examine the robustness of the method using different priors corresponding to different degrees of confidence in the testing results and propose a Bayesian model averaging procedure to combine estimates produced by different models. The Bayesian estimators yield smaller variance compared to the conditional likelihood estimator and outperform the latter in studies with low power. We investigate the performance of the method with simulations and applications to four real data examples.

Full work available at URL: https://arxiv.org/abs/0907.2770

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zbMATH Keywords

Bayesian model averagingassociation studyhierarchical Bayes modelspike-and-slab prior

Mathematics Subject Classification ID

Point estimation (62F10) Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Genetics and epigenetics (92D10)

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Cited In (5)

• A Bayesian model averaging approach for observational gene expression studies
• The significance filter, the winner's curse and the need to shrink
• Estimation of genetic effects incorporating prior information
• Bayesian Methods for Examining Hardy-Weinberg Equilibrium
• Title not available (Why is that?)

Uses Software

• tsbridge

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