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Using Gene Genealogies to Localize Rare Variants Associated with Complex Traits in Diploid Populations.
Human Heredity ( IF 1.8 ) Pub Date : 2018-05-16 , DOI: 10.1159/000486854
Charith B. Karunarathna , Jinko Graham

BACKGROUND AND AIMS Many methods can detect trait association with causal variants in candidate genomic regions; however, a comparison of their ability to localize causal variants is lacking. We extend a previous study of the detection abilities of these methods to a comparison of their localization abilities. METHODS Through coalescent simulation, we compare several popular association methods. Cases and controls are sampled from a diploid population to mimic human studies. As benchmarks for comparison, we include two methods that cluster phenotypes on the true genealogical trees: a naive Mantel test considered previously in haploid populations and an extension that takes into account whether case haplotypes carry a causal variant. We first work through a simulated dataset to illustrate the methods. We then perform a simulation study to score the localization and detection properties. RESULTS In our simulations, the association signal was localized least precisely by the naive Mantel test and most precisely by its extension. Most other approaches had intermediate performance similar to the single-variant Fisher exact test. CONCLUSIONS Our results confirm earlier findings in haploid populations about potential gains in performance from genealogy-based approaches. They also highlight differences between haploid and diploid populations when localizing and detecting causal variants.

中文翻译:

使用基因谱系来定位与二倍体群体中的复杂性状相关的稀有变异。

背景和目的许多方法都可以检测候选基因组区域中与因果变异相关的性状。然而,他们缺乏对因果变量进行定位的能力的比较。我们将这些方法的检测能力的先前研究扩展到它们的定位能力的比较。方法通过合并模拟,我们比较了几种流行的关联方法。从二倍体人群中抽取病例和对照来模拟人类研究。作为比较的基准,我们包括两种在真实家谱树上聚集表型的方法:以前在单倍体种群中考虑过的朴素Mantel检验和考虑案例单倍型是否携带因果变异的扩展。我们首先通过模拟数据集来说明这些方法。然后,我们执行模拟研究以对定位和检测属性进行评分。结果在我们的模拟中,关联信号通过朴素的Mantel测试定位得最不准确,而通过扩展则定位得最精确。大多数其他方法具有类似于单变量Fisher精确检验的中间性能。结论我们的研究结果证实了单倍体群体中有关基于家谱方法的潜在潜在收益的发现。当定位和检测因果变异时,它们还突出了单倍体和二倍体种群之间的差异。大多数其他方法具有类似于单变量Fisher精确检验的中间性能。结论我们的研究结果证实了单倍体群体中有关基于家谱方法的潜在潜在收益的发现。当定位和检测因果变异时,它们还突出了单倍体和二倍体种群之间的差异。大多数其他方法具有类似于单变量Fisher精确检验的中间性能。结论我们的研究结果证实了单倍体群体中有关基于家谱方法的潜在潜在收益的发现。当定位和检测因果变异时,它们还突出了单倍体和二倍体种群之间的差异。
更新日期:2019-11-01
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