A robust distribution-free test for genetic association studies of quantitative traits

Kozlitina Julia () and Schucany William R.
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Kozlitina Julia: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8591, USA
Schucany William R.: Department of Statistical Science, Southern Methodist University, Dallas, TX, USA (Emeritus)

Statistical Applications in Genetics and Molecular Biology, 2015, vol. 14, issue 5, 443-464

Abstract: In association studies of quantitative traits, the association of each genetic marker with the trait of interest is typically tested using the F-test assuming an additive genetic model. In practice, the true model is rarely known, and specifying an incorrect model can lead to a loss of power. For case-control studies, the maximum of test statistics optimal for additive, dominant, and recessive models has been shown to be robust to model misspecification. The approach has later been extended to quantitative traits. However, the existing procedures assume that the trait is normally distributed and may not maintain correct type I error rates and can also have reduced power when the assumption of normality is violated. Here, we introduce a maximum (MAX3) test that is based on ranks and is therefore distribution-free. We examine the behavior of the proposed method using a Monte Carlo simulation with both normal and non-normal data and compare the results to the usual parametric procedures and other nonparametric alternatives. We show that the rank-based maximum test has favorable properties relative to other tests, especially in the case of symmetric distributions with heavy tails. We illustrate the method with data from a real association study of symmetric dimethylarginine (SDMA).

Keywords: maximum (MAX) test; model uncertainty and misspecification; non-normal data; order-restricted inference; power; rank tests for trend (search for similar items in EconPapers)
Date: 2015
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DOI: 10.1515/sagmb-2014-0050

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