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首页> 外文期刊>Annals of Human Genetics >Power of Genetic Association Studies with Fixed and Random Genotype Frequencies
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Power of Genetic Association Studies with Fixed and Random Genotype Frequencies

机译：固定和随机基因型频率的遗传关联研究的力量

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When estimating the power of genetic association studies, the allele and genotype frequencies are often assumed to be known, and the numbers of individuals with each genotype are set equal to their expectations under Hardy-Weinberg equilibrium. In fact, both allele and genotype frequencies are unknown and thus random. It has previously been suggested that ignoring uncertainty in these parameters could lead to inflated power expectations. To overcome the problem, one can average power estimates over the distributions of unknown frequencies. We investigate the power-averaging method and find that, despite the intuitive appeal, it may not improve accuracy in practice, while significantly increasing computational time. For a fixed allele frequency, we show that the amount of overestimation diminishes rapidly with sample size and is completely negligible for N > 200. For an unknown frequency, the result of averaging depends on the genetic model, and may not always provide a more conservative estimate of power. We explore the effect of uncertainty in the factors that determine statistical power of association studies and propose a more economical approach to the power analysis.
机译：在评估遗传关联研究的能力时，通常假定等位基因和基因型频率已知，并且在Hardy-Weinberg平衡下，每种基因型的个体数量均设为其期望值。实际上，等位基因频率和基因型频率都是未知的，因此是随机的。以前曾有人提出，忽略这些参数的不确定性可能会导致功率预期过高。为了克服这个问题，可以对未知频率的分布进行平均功率估计。我们研究了功率平均方法，发现尽管具有直观的吸引力，但它可能无法提高实践中的准确性，同时会显着增加计算时间。对于固定的等位基因频率，我们显示高估量随样本数量的增加而迅速减少，并且对于N> 200可以完全忽略不计。对于未知频率，平均结果取决于遗传模型，可能并不总是提供更保守的结果估计功率。我们探讨了不确定性在确定关联研究的统计功效的因素中的作用，并提出了一种更经济的功效分析方法。

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