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 journalArticle

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.

LanguageEnglish (US)
Pages155-167
Number of pages13
JournalBehavior Genetics
Volume48
Issue number2
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Fingerprint

phenotype
inflation
Phenotype
Genome-Wide Association Study
Economic Inflation
confidence interval
methodology
method
testing
Confidence Intervals

Keywords

  • Complex traits
  • Multivariate GWAS
  • TATES

ASJC Scopus subject areas

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

Cite this

Aliev, F., Salvatore, J. E., Agrawal, A., Almasy, L., Chan, G., Edenberg, H. J., ... Dick, D. M. (2018). A Brief Critique of the TATES Procedure. Behavior Genetics, 48(2), 155-167. https://doi.org/10.1007/s10519-018-9890-6

A Brief Critique of the TATES Procedure. / Aliev, Fazil; Salvatore, Jessica E.; Agrawal, Arpana; Almasy, Laura; Chan, Grace; Edenberg, Howard J.; Hesselbrock, Victor; Kuperman, Samuel; Meyers, Jacquelyn; Dick, Danielle M.

In: Behavior Genetics, Vol. 48, No. 2, 01.03.2018, p. 155-167.

Research output: Contribution to journalArticle

Aliev, F, Salvatore, JE, Agrawal, A, Almasy, L, Chan, G, Edenberg, HJ, Hesselbrock, V, Kuperman, S, Meyers, J & Dick, DM 2018, 'A Brief Critique of the TATES Procedure' Behavior Genetics, vol. 48, no. 2, pp. 155-167. https://doi.org/10.1007/s10519-018-9890-6
Aliev F, Salvatore JE, Agrawal A, Almasy L, Chan G, Edenberg HJ et al. A Brief Critique of the TATES Procedure. Behavior Genetics. 2018 Mar 1;48(2):155-167. https://doi.org/10.1007/s10519-018-9890-6
Aliev, Fazil ; Salvatore, Jessica E. ; Agrawal, Arpana ; Almasy, Laura ; Chan, Grace ; Edenberg, Howard J. ; Hesselbrock, Victor ; Kuperman, Samuel ; Meyers, Jacquelyn ; Dick, Danielle M. / A Brief Critique of the TATES Procedure. In: Behavior Genetics. 2018 ; Vol. 48, No. 2. pp. 155-167.
@article{cd2d11ff85da4774ad6157b549deff36,
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.",
keywords = "Complex traits, Multivariate GWAS, TATES",
author = "Fazil Aliev and Salvatore, {Jessica E.} and Arpana Agrawal and Laura Almasy and Grace Chan and Edenberg, {Howard J.} and Victor Hesselbrock and Samuel Kuperman and Jacquelyn Meyers and Dick, {Danielle M.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1007/s10519-018-9890-6",
language = "English (US)",
volume = "48",
pages = "155--167",
journal = "Behavior Genetics",
issn = "0001-8244",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - A Brief Critique of the TATES Procedure

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.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

KW - Complex traits

KW - Multivariate GWAS

KW - TATES

UR - http://www.scopus.com/inward/record.url?scp=85042230410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042230410&partnerID=8YFLogxK

U2 - 10.1007/s10519-018-9890-6

DO - 10.1007/s10519-018-9890-6

M3 - Article

VL - 48

SP - 155

EP - 167

JO - Behavior Genetics

T2 - Behavior Genetics

JF - Behavior Genetics

SN - 0001-8244

IS - 2

ER -