Graphical-model based multiple testing under dependence, with applications to genome-wide association studies

Jie Liu, Peggy Peissig, Chunming Zhang, Elizabeth Burnside, Catherine McCarty, David Page

Research output: Chapter in Book/Report/Conference proceedingConference contribution

4 Scopus citations

Abstract

Large-scale multiple testing tasks often exhibit dependence, and leveraging the dependence between individual tests is still one challenging and important problem in statistics. With recent advances in graphical models, it is feasible to use them to perform multiple testing under dependence. We propose a multiple testing procedure which is based on a Markov-random-field-coupled mixture model. The ground truth of hypotheses is represented by a latent binary Markov random field, and the observed test statistics appear as the coupled mixture variables. The parameters in our model can be automatically learned by a novel EM algorithm. We use an MCMC algorithm to infer the posterior probability that each hypothesis is null (termed local index of significance), and the false discovery rate can be controlled accordingly. Simulations show that the numerical performance of multiple testing can be improved substantially by using our procedure. We apply the procedure to a real-world genome-wide association study on breast cancer, and we identify several SNPs with strong association evidence.

Original languageEnglish (US)
Title of host publicationUncertainty in Artificial Intelligence - Proceedings of the 28th Conference, UAI 2012
Pages511-522
Number of pages12
StatePublished - Dec 1 2012
Event28th Conference on Uncertainty in Artificial Intelligence, UAI 2012 - Catalina Island, CA, United States
Duration: Aug 15 2012Aug 17 2012

Publication series

NameUncertainty in Artificial Intelligence - Proceedings of the 28th Conference, UAI 2012

Other

Other28th Conference on Uncertainty in Artificial Intelligence, UAI 2012
CountryUnited States
CityCatalina Island, CA
Period8/15/128/17/12

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