SNP Selection and Multidimensional Scaling to Quantify Population Structure
SNP Selection and Multidimensional Scaling to Quantify Population Structure
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DOI：
10.1002/gepi.20401
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发表时间：
2009-09-01
影响因子：
2.1
通讯作者：
Czika, Wendy
中科院分区：
文献类型：
--
作者：
Miclaus, Kelci;Wolfinger, Russ;Czika, Wendy
在大规模协同全基因组关联研究（GWAS）的新时代，种群分层已成为一个必须解决的关键问题。为了建立控制结构种群混杂效应的方法，可视化和量化这种效应是极其重要的。在这项工作中，我们开发了基于Hardy-Weinberg平衡偏差和非度量多维标度（MDS）的单核苷酸多态性（SNP）选择和随后的群体分层可视化方法；基于距离的多变量技术。通过模拟，表明基于Hardy-Weinberg不平衡（HWD）的SNP选择对混杂的连锁不平衡模式具有鲁棒性，这些模式在过去的研究和方法中一直存在问题，并产生差异化的SNP集。通过对HapMap样本的理论和实证研究，非度量MDS被证明是一种多变量可视化工具，比主成分与HWD SNP选择更可取。所提出的选择工具提供了一种简单有效的方法来选择适当的子结构信息标记，用于探索群体分层在关联研究中可能产生的影响。麝猫。流行病学杂志，2009,33:488-496。(C) 2009 Wiley-Liss, Inc。
In the new era of large-scale collaborative Genome Wide Association Studies (GWAS), population stratification has become a critical issue that must be addressed. In order to build upon the methods developed to control the confounding effect of a structured population, it is extremely important to visualize and quantify that effect. In this work, we develop methodology for single nucleotide polymorphism (SNP) selection and subsequent population stratification visualization based on deviation from Hardy-Weinberg equilibrium in conjunction with non-metric multidimensional scaling (MDS); a distance-based multivariate technique. Through simulation, it is shown that SNP selection based on Hardy-Weinberg disequilibrium (HWD) is robust against confounding linkage disequilibrium patterns that have been problematic in past studies and methods as well as producing a differentiated SNP set. Non-metric MDS is shown to be a multivariate visualization tool preferable to principal components in conjunction with HWD SNP selection through theoretical and empirical study from HapMap samples. The proposed selection tool offers a simple and effective way to select appropriate substructure-informative markers for use in exploring the effect that population stratification may have in association studies. Genet. Epidemiol. 33:488-496, 2009. (C) 2009 Wiley-Liss, Inc.