A unified framework for association analysis with multiple related phenotypes.

A unified framework for association analysis with multiple related phenotypes.
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与多种相关表型的关联分析的统一框架。

DOI:
10.1371/journal.pone.0065245
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Stephens M
Stephens M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Stephens M

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我们考虑的问题,评估多个相关的结果变量之间的关联,和一个单一的解释变量的利益。这个问题出现在许多环境中,包括遗传关联研究,其中解释变量是遗传变异的基因型。我们概述了进行这种类型的分析框架,基于贝叶斯模型比较和模型平均多元回归。这个框架统一了几种常见的方法来解决这个问题,并包括标准的单变量和标准的多变量关联测试作为特殊情况。该框架还统一了检验关联和解释关联的问题,即确定哪些结果变量与基因型相关。这提供了一种替代通常的,但概念上不满意,诉诸单变量检验的方法时,解释和解释显着的多变量结果。该方法对于适度数量的表型(例如5-10)在全基因组范围内是计算上易处理的,并且可以应用于汇总数据,而无需访问原始基因型和表型数据。我们说明了这两个模拟的例子的方法,并在全基因组关联研究的血脂性状,我们确定了18个潜在的新的遗传协会,没有确定的单变量分析相同的数据。
We consider the problem of assessing associations between multiple related outcome variables, and a single explanatory variable of interest. This problem arises in many settings, including genetic association studies, where the explanatory variable is genotype at a genetic variant. We outline a framework for conducting this type of analysis, based on Bayesian model comparison and model averaging for multivariate regressions. This framework unifies several common approaches to this problem, and includes both standard univariate and standard multivariate association tests as special cases. The framework also unifies the problems of testing for associations and explaining associations – that is, identifying which outcome variables are associated with genotype. This provides an alternative to the usual, but conceptually unsatisfying, approach of resorting to univariate tests when explaining and interpreting significant multivariate findings. The method is computationally tractable genome-wide for modest numbers of phenotypes (e.g. 5–10), and can be applied to summary data, without access to raw genotype and phenotype data. We illustrate the methods on both simulated examples, and to a genome-wide association study of blood lipid traits where we identify 18 potential novel genetic associations that were not identified by univariate analyses of the same data.
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