Abstract
Quantitative trait locus analysis has been used as an important tool to identify markers where the phenotype or quantitative trait is linked with the genotype. Most existing tests for single locus association with quantitative traits aim at the detection of the mean differences across genotypic groups. However, recent research has revealed functional genetic loci that affect the variance of traits, known as variability-controlling quantitative trait locus. In addition, it has been suggested that many genotypes have both mean and variance effects, while the mean effects or variance effects alone may not be strong enough to be detected. The existing methods accounting for unequal variances include the Levene's test, the Lepage test, and the D-test, but suffer from their limitations of lack of robustness or lack of power. We propose a semiparametric model and a novel pairwise conditional likelihood ratio test. Specifically, the semiparametric model is designed to identify the combined differences in higher moments among genotypic groups. The pairwise likelihood is constructed based on conditioning procedure, where the unknown reference distribution is eliminated. We show that the proposed pairwise likelihood ratio test has a simple asymptotic chi-square distribution, which does not require permutation or bootstrap procedures. Simulation studies show that the proposed test performs well in controlling Type I errors and having competitive power in identifying the differences across genotypic groups. In addition, the proposed test has certain robustness to model mis-specifications. The proposed test is illustrated by an example of identifying both mean and variances effects in body mass index using the Framingham Heart Study data.
Original language | English (US) |
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Pages (from-to) | 571-581 |
Number of pages | 11 |
Journal | Biometrics |
Volume | 73 |
Issue number | 2 |
DOIs | |
State | Published - Jun 2017 |
Keywords
- Composite likelihood
- Conditional likelihood
- Exponential tilt model
- Pseudolikelihood
- Semiparametric model
- VQTL
ASJC Scopus subject areas
- Statistics and Probability
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- General Agricultural and Biological Sciences
- Applied Mathematics
MD Anderson CCSG core facilities
- Biostatistics Resource Group