Estimation and testing for multiple regulation of multivariate mixed outcomes

DOI10.1111/BIOM.12495MaRDI QIDQ5355243zbMATH OpenOpenAlexWikidataFDO

Authors Denis Agniel, Katherine P. Liao, Tianxi Cai

Publication date 7 September 2017

Published in Biometrics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1511.08074, http://europepmc.org/articles/pmc5459434

zbMATH Keywords

multiple testingresamplingsemiparametric modelsmultiple phenotypeshierarchical Lassofamilywise error controlmultiple regulationstepdown testing

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Nonparametric statistical resampling methods (62G09) Estimation in multivariate analysis (62H12) Ridge regression; shrinkage estimators (Lasso) (62J07)

Abstract: Considerable interest has recently been focused on studying multiple phenotypes simultaneously in both epidemiological and genomic studies, either to capture the multidimensionality of complex disorders or to understand shared etiology of related disorders. We seek to identify {em multiple regulators} or predictors that are associated with multiple outcomes when these outcomes may be measured on very different scales or composed of a mixture of continuous, binary, and not-fully-observed elements. We first propose an estimation technique to put all effects on similar scales, and we induce sparsity on the estimated effects. We provide standard asymptotic results for this estimator and show that resampling can be used to quantify uncertainty in finite samples. We finally provide a multiple testing procedure which can be geared specifically to the types of multiple regulators of interest, and we establish that, under standard regularity conditions, the familywise error rate will approach 0 as sample size diverges. Simulation results indicate that our approach can improve over unregularized methods both in reducing bias in estimation and improving power for testing.

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• A Scaled Linear Mixed Model for Multiple Outcomes
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• Joint regression analysis of mixed-type outcome data via efficient scores
• A multivariate Wilcoxon regression estimate
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• Analysis of multiple diverse phenotypes via semiparametric canonical correlation analysis

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