Rare variants detection with kernel machine learning based on likelihood ratio test.
This paper mainly utilizes likelihood-based tests to detect rare variants associated with a continuous phenotype under the framework of kernel machine learning. Both the likelihood ratio test (LRT) and the restricted likelihood ratio test (ReLRT) are investigated. The relationship between the kernel...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3968153?pdf=render |
id |
doaj-fe5b0c7363bc416691b47abfc0ae4d4d |
---|---|
record_format |
Article |
spelling |
doaj-fe5b0c7363bc416691b47abfc0ae4d4d2020-11-24T21:50:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9335510.1371/journal.pone.0093355Rare variants detection with kernel machine learning based on likelihood ratio test.Ping ZengYang ZhaoLiwei ZhangShuiping HuangFeng ChenThis paper mainly utilizes likelihood-based tests to detect rare variants associated with a continuous phenotype under the framework of kernel machine learning. Both the likelihood ratio test (LRT) and the restricted likelihood ratio test (ReLRT) are investigated. The relationship between the kernel machine learning and the mixed effects model is discussed. By using the eigenvalue representation of LRT and ReLRT, their exact finite sample distributions are obtained in a simulation manner. Numerical studies are performed to evaluate the performance of the proposed approaches under the contexts of standard mixed effects model and kernel machine learning. The results have shown that the LRT and ReLRT can control the type I error correctly at the given α level. The LRT and ReLRT consistently outperform the SKAT, regardless of the sample size and the proportion of the negative causal rare variants, and suffer from fewer power reductions compared to the SKAT when both positive and negative effects of rare variants are present. The LRT and ReLRT performed under the context of kernel machine learning have slightly higher powers than those performed under the context of standard mixed effects model. We use the Genetic Analysis Workshop 17 exome sequencing SNP data as an illustrative example. Some interesting results are observed from the analysis. Finally, we give the discussion.http://europepmc.org/articles/PMC3968153?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ping Zeng Yang Zhao Liwei Zhang Shuiping Huang Feng Chen |
spellingShingle |
Ping Zeng Yang Zhao Liwei Zhang Shuiping Huang Feng Chen Rare variants detection with kernel machine learning based on likelihood ratio test. PLoS ONE |
author_facet |
Ping Zeng Yang Zhao Liwei Zhang Shuiping Huang Feng Chen |
author_sort |
Ping Zeng |
title |
Rare variants detection with kernel machine learning based on likelihood ratio test. |
title_short |
Rare variants detection with kernel machine learning based on likelihood ratio test. |
title_full |
Rare variants detection with kernel machine learning based on likelihood ratio test. |
title_fullStr |
Rare variants detection with kernel machine learning based on likelihood ratio test. |
title_full_unstemmed |
Rare variants detection with kernel machine learning based on likelihood ratio test. |
title_sort |
rare variants detection with kernel machine learning based on likelihood ratio test. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
This paper mainly utilizes likelihood-based tests to detect rare variants associated with a continuous phenotype under the framework of kernel machine learning. Both the likelihood ratio test (LRT) and the restricted likelihood ratio test (ReLRT) are investigated. The relationship between the kernel machine learning and the mixed effects model is discussed. By using the eigenvalue representation of LRT and ReLRT, their exact finite sample distributions are obtained in a simulation manner. Numerical studies are performed to evaluate the performance of the proposed approaches under the contexts of standard mixed effects model and kernel machine learning. The results have shown that the LRT and ReLRT can control the type I error correctly at the given α level. The LRT and ReLRT consistently outperform the SKAT, regardless of the sample size and the proportion of the negative causal rare variants, and suffer from fewer power reductions compared to the SKAT when both positive and negative effects of rare variants are present. The LRT and ReLRT performed under the context of kernel machine learning have slightly higher powers than those performed under the context of standard mixed effects model. We use the Genetic Analysis Workshop 17 exome sequencing SNP data as an illustrative example. Some interesting results are observed from the analysis. Finally, we give the discussion. |
url |
http://europepmc.org/articles/PMC3968153?pdf=render |
work_keys_str_mv |
AT pingzeng rarevariantsdetectionwithkernelmachinelearningbasedonlikelihoodratiotest AT yangzhao rarevariantsdetectionwithkernelmachinelearningbasedonlikelihoodratiotest AT liweizhang rarevariantsdetectionwithkernelmachinelearningbasedonlikelihoodratiotest AT shuipinghuang rarevariantsdetectionwithkernelmachinelearningbasedonlikelihoodratiotest AT fengchen rarevariantsdetectionwithkernelmachinelearningbasedonlikelihoodratiotest |
_version_ |
1725883305691185152 |