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.
| Language | English (US) |
|---|---|
| Pages | 155-167 |
| Number of pages | 13 |
| Journal | Behavior Genetics |
| Volume | 48 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2018 |
| Externally published | Yes |
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Keywords
- Complex traits
- Multivariate GWAS
- TATES
ASJC Scopus subject areas
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Genetics(clinical)
Cite this
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 journal › Article
}
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 -