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Sequence Kernel Association Test for Survival Traits
Author(s) -
Chen Han,
Lumley Thomas,
Brody Jennifer,
HeardCosta Nancy L.,
Fox Caroline S.,
Cupples L. Adrienne,
Dupuis Josée
Publication year - 2014
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21791
Subject(s) - statistics , test statistic , type i and type ii errors , logistic regression , score test , likelihood ratio test , kernel (algebra) , sample size determination , mathematics , statistical hypothesis testing , combinatorics
Rare variant tests have been of great interest in testing genetic associations with diseases and disease‐related quantitative traits in recent years. Among these tests, the sequence kernel association test (SKAT) is an omnibus test for effects of rare genetic variants, in a linear or logistic regression framework. It is often described as a variance component test treating the genotypic effects as random. When the linear kernel is used, its test statistic can be expressed as a weighted sum of single‐marker score test statistics. In this paper, we extend the test to survival phenotypes in a Cox regression framework. Because of the anticonservative small‐sample performance of the score test in a Cox model, we substitute signed square‐root likelihood ratio statistics for the score statistics, and confirm that the small‐sample control of type I error is greatly improved. This test can also be applied in meta‐analysis. We show in our simulation studies that this test has superior statistical power except in a few specific scenarios, as compared to burden tests in a Cox model. We also present results in an application to time‐to‐obesity using genotypes from Framingham Heart Study SNP Health Association Resource.