A Brief Critique of the TATES Procedure

Fazil Aliev; Jessica E. Salvatore; Arpana Agrawal; Laura Almasy; Grace Chan; Howard J. Edenberg; Victor Hesselbrock; Samuel Kuperman; Jacquelyn Meyers; Danielle M. Dick

doi:10.1007/s10519-018-9890-6

A Brief Critique of the TATES Procedure

Fazil Aliev, Jessica E. Salvatore, Arpana Agrawal, Laura Almasy, Grace Chan, Howard J. Edenberg, Victor Hesselbrock, Samuel Kuperman, Jacquelyn Meyers, Danielle M. Dick

Research output: Contribution to journal › Article › peer-review

Abstract

The Trait-based test that uses the Extended Simes procedure (TATES) was developed as a method for conducting multivariate GWAS for correlated phenotypes whose underlying genetic architecture is complex. In this paper, we provide a brief methodological critique of the TATES method using simulated examples and a mathematical proof. Our simulated examples using correlated phenotypes show that the Type I error rate is higher than expected, and that more TATES p values fall outside of the confidence interval relative to expectation. Thus the method may result in systematic inflation when used with correlated phenotypes. In a mathematical proof we further demonstrate that the distribution of TATES p values deviates from expectation in a manner indicative of inflation. Our findings indicate the need for caution when using TATES for multivariate GWAS of correlated phenotypes.

Original language	English (US)
Pages (from-to)	155-167
Number of pages	13
Journal	Behavior Genetics
Volume	48
Issue number	2
DOIs	https://doi.org/10.1007/s10519-018-9890-6
State	Published - Mar 1 2018
Externally published	Yes

Keywords

Complex traits
Multivariate GWAS
TATES

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Genetics(clinical)

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title = "A Brief Critique of the TATES Procedure",

abstract = "The Trait-based test that uses the Extended Simes procedure (TATES) was developed as a method for conducting multivariate GWAS for correlated phenotypes whose underlying genetic architecture is complex. In this paper, we provide a brief methodological critique of the TATES method using simulated examples and a mathematical proof. Our simulated examples using correlated phenotypes show that the Type I error rate is higher than expected, and that more TATES p values fall outside of the confidence interval relative to expectation. Thus the method may result in systematic inflation when used with correlated phenotypes. In a mathematical proof we further demonstrate that the distribution of TATES p values deviates from expectation in a manner indicative of inflation. Our findings indicate the need for caution when using TATES for multivariate GWAS of correlated phenotypes.",

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AU - Aliev, Fazil

AU - Salvatore, Jessica E.

AU - Agrawal, Arpana

AU - Almasy, Laura

AU - Chan, Grace

AU - Edenberg, Howard J.

AU - Hesselbrock, Victor

AU - Kuperman, Samuel

AU - Meyers, Jacquelyn

AU - Dick, Danielle M.

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