A Brief Critique of the TATES Procedure
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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.
KeywordsMultivariate GWAS Complex traits TATES
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.
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Conflict of interest
Fazil Aliev, Jessica E. Salvatore, Arpana Agrawal, Laura Almasy, Grace Chan, Howard J. Edenberg, Victor Hesselbrock, Samuel Kuperman, Jacquelyn Meyers and Danielle M. Dick declare that they have no conflicts of interest.
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