Published January 1, 2018
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A Brief Critique of the TATES Procedure
Creators
- 1. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
- 2. Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA
- 3. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA
- 4. Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA
- 5. Univ Iowa Hosp, Div Child Psychiat, Iowa City, IA USA
- 6. Suny Downstate Med Ctr, Dept Psychiat, New York, NY USA
Description
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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