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)

Access to Document

10.1007/s10519-018-9890-6

Fingerprint Dive into the research topics of 'A Brief Critique of the TATES Procedure'. Together they form a unique fingerprint.

Cite this

@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.}",

note = "Funding Information: Acknowledgements This work was supported in part by funding for The Collaborative Study on the Genetics of Alcoholism, NIH Grant U10AA008401. This work was also supported by F32AA022269 and K01AA024152 (Salvatore); TUBITAK, Turkey, Grant #114C117 (Aliev); K02AA018755 (Dick); and DA32573 (Agrawal). This publication is solely the responsibility of the authors and does not necessarily represent the official view of the funders.",

year = "2018",

month = mar,

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.

N1 - Funding Information: Acknowledgements This work was supported in part by funding for The Collaborative Study on the Genetics of Alcoholism, NIH Grant U10AA008401. This work was also supported by F32AA022269 and K01AA024152 (Salvatore); TUBITAK, Turkey, Grant #114C117 (Aliev); K02AA018755 (Dick); and DA32573 (Agrawal). This publication is solely the responsibility of the authors and does not necessarily represent the official view of the funders.

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

C2 - 29468442

AN - SCOPUS:85042230410

VL - 48

SP - 155

EP - 167

JO - Behavior Genetics

JF - Behavior Genetics

SN - 0001-8244

IS - 2

ER -

A Brief Critique of the TATES Procedure

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this