A variational Bayes algorithm for fast and accurate multiple locus genome-wide association analysis.

A variational Bayes algorithm for fast and accurate multiple locus genome-wide association analysis.
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DOI:
10.1186/1471-2105-11-58
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发表时间:
2010-01-27
期刊:
影响因子:
3
通讯作者:
Mezey JG
Mezey JG
中科院分区:
生物学4区
文献类型:
--
作者:
Logsdon BA;Hoffman GE;Mezey JG

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全基因组关联(GWA)研究在鉴定复杂疾病的候选基因座方面取得了成功,但与此同时,却无法解释大部分遗传力。在此,我们描述了V - Bay算法,这是一种用于多位点GWA分析的变分贝叶斯算法,旨在识别可能导致这种缺失遗传力的较弱关联。 V - Bay为大多数多位点方法的计算规模限制提供了一种新的解决方案,当使用台式机时,它能够在几小时内完成对一百万个遗传标记的同时分析。通过一系列模拟的遗传和GWA实验场景,我们证明V - Bay具有很高的准确性,并且能够可靠地识别那些太弱而无法被单标记检测方法发现的关联。V - Bay还能优于一种基于套索(lasso)的多位点分析方法,该方法对于大量遗传标记具有相似的规模特性。出于演示目的,我们还使用V - Bay确认了与来自国际人类基因组单体型图计划(HapMap)二期个体的细胞系中基因表达的关联。 对于有兴趣识别较弱关联且不产生高假阳性率的研究者来说,V - Bay是一种通用、快速且准确的多位点GWA分析工具。
The success achieved by genome-wide association (GWA) studies in the identification of candidate loci for complex diseases has been accompanied by an inability to explain the bulk of heritability. Here, we describe the algorithm V-Bay, a variational Bayes algorithm for multiple locus GWA analysis, which is designed to identify weaker associations that may contribute to this missing heritability. V-Bay provides a novel solution to the computational scaling constraints of most multiple locus methods and can complete a simultaneous analysis of a million genetic markers in a few hours, when using a desktop. Using a range of simulated genetic and GWA experimental scenarios, we demonstrate that V-Bay is highly accurate, and reliably identifies associations that are too weak to be discovered by single-marker testing approaches. V-Bay can also outperform a multiple locus analysis method based on the lasso, which has similar scaling properties for large numbers of genetic markers. For demonstration purposes, we also use V-Bay to confirm associations with gene expression in cell lines derived from the Phase II individuals of HapMap. V-Bay is a versatile, fast, and accurate multiple locus GWA analysis tool for the practitioner interested in identifying weaker associations without high false positive rates.
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