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Rare variant association tests for ancestry-matched case-control data based on conditional logistic regression.

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单位: [1]Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China. [2]Center for Quantitative Biology, Peking University, Beijing 100871, P. R. China. [3]LMAM, School of Mathematical Sciences, Peking University, Beijing 100871, P. R. China. [4]Center for Statistical Sciences, Peking University, Beijing 100871, P. R. China. [5]Department of Statistics and Data Science, National University of Singapore, Singapore 117546, Singapore. [6]Department of Orthopedic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,P.R. China.
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With the increasing volume of human sequencing data available, analysis incorporating external controls becomes a popular and cost-effective approach to boost statistical power in disease association studies. To prevent spurious association due to population stratification, it is important to match the ancestry backgrounds of cases and controls. However, rare variant association tests based on a standard logistic regression model are conservative when all ancestry-matched strata have the same case-control ratio and might become anti-conservative when case-control ratio varies across strata. Under the conditional logistic regression (CLR) model, we propose a weighted burden test (CLR-Burden), a variance component test (CLR-SKAT) and a hybrid test (CLR-MiST). We show that the CLR model coupled with ancestry matching is a general approach to control for population stratification, regardless of the spatial distribution of disease risks. Through extensive simulation studies, we demonstrate that the CLR-based tests robustly control type 1 errors under different matching schemes and are more powerful than the standard Burden, SKAT and MiST tests. Furthermore, because CLR-based tests allow for different case-control ratios across strata, a full-matching scheme can be employed to efficiently utilize all available cases and controls to accelerate the discovery of disease associated genes.© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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出版当年[2021]版
大类 | 2 区 生物学
小类 | 2 区 生化研究方法 2 区 数学与计算生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 1 区 数学与计算生物学 2 区 生化研究方法
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第一作者单位: [1]Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
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