Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Likelihood Ratio Tests in Rare Variant Detection for Continuous Phenotypes

Likelihood Ratio Tests in Rare Variant Detection for Continuous Phenotypes It is believed that rare variants play an important role in human phenotypes; however, the detection of rare variants is extremely challenging due to their very low minor allele frequency. In this paper, the likelihood ratio test (LRT) and restricted likelihood ratio test (ReLRT) are proposed to test the association of rare variants based on the linear mixed effects model, where a group of rare variants are treated as random effects. Like the sequence kernel association test (SKAT), a state‐of‐the‐art method for rare variant detection, LRT and ReLRT can effectively overcome the problem of directionality of effect inherent in the burden test in practice. By taking full advantage of the spectral decomposition, exact finite sample null distributions for LRT and ReLRT are obtained by simulation. We perform extensive numerical studies to evaluate the performance of LRT and ReLRT, and compare to the burden test, SKAT and SKAT‐O. The simulations have shown that LRT and ReLRT can correctly control the type I error, and the controls are robust to the weights chosen and the number of rare variants under study. LRT and ReLRT behave similarly to the burden test when all the causal rare variants share the same direction of effect, and outperform SKAT across various situations. When both positive and negative effects exist, LRT and ReLRT suffer from few power reductions compared to the other two competing methods; under this case, an additional finding from our simulations is that SKAT‐O is no longer the optimal test, and its power is even lower than that of SKAT. The exome sequencing SNP data from Genetic Analysis Workshop 17 were employed to illustrate the proposed methods, and interesting results are described. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

Likelihood Ratio Tests in Rare Variant Detection for Continuous Phenotypes

Download PDF
13 pages

Loading next page...
 
/lp/wiley/likelihood-ratio-tests-in-rare-variant-detection-for-continuous-jn09HZJed6

References (60)

Publisher
Wiley
Copyright
Copyright © 2014 John Wiley & Sons Ltd/University College London
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1111/ahg.12071
pmid
25117149
Publisher site
See Article on Publisher Site

Abstract

It is believed that rare variants play an important role in human phenotypes; however, the detection of rare variants is extremely challenging due to their very low minor allele frequency. In this paper, the likelihood ratio test (LRT) and restricted likelihood ratio test (ReLRT) are proposed to test the association of rare variants based on the linear mixed effects model, where a group of rare variants are treated as random effects. Like the sequence kernel association test (SKAT), a state‐of‐the‐art method for rare variant detection, LRT and ReLRT can effectively overcome the problem of directionality of effect inherent in the burden test in practice. By taking full advantage of the spectral decomposition, exact finite sample null distributions for LRT and ReLRT are obtained by simulation. We perform extensive numerical studies to evaluate the performance of LRT and ReLRT, and compare to the burden test, SKAT and SKAT‐O. The simulations have shown that LRT and ReLRT can correctly control the type I error, and the controls are robust to the weights chosen and the number of rare variants under study. LRT and ReLRT behave similarly to the burden test when all the causal rare variants share the same direction of effect, and outperform SKAT across various situations. When both positive and negative effects exist, LRT and ReLRT suffer from few power reductions compared to the other two competing methods; under this case, an additional finding from our simulations is that SKAT‐O is no longer the optimal test, and its power is even lower than that of SKAT. The exome sequencing SNP data from Genetic Analysis Workshop 17 were employed to illustrate the proposed methods, and interesting results are described.

Journal

Annals of Human Genetics – Wiley

Published: Jan 1, 2014

Keywords: ; ; ; ; ; ;

There are no references for this article.