Detecting positive selection from genome scans of linkage disequilibrium.
Detecting positive selection from genome scans of linkage disequilibrium.
复制标题
DOI：
10.1186/1471-2164-11-8
复制
发表时间：
2010-01-05
期刊：
影响因子：
4.4
通讯作者：
Rogers AR
中科院分区：
文献类型：
--
作者：
Huff CD;Harpending HC;Rogers AR
虽然最近引入了各种连锁不平衡检验来衡量最近正选择的信号，但各种方法的统计性质还没有被直接比较。虽然这些测试的大多数应用表明，积极选择在近代史上发挥了重要作用，但这些测试的结果差异很大。在这里，我们评估三种统计量的性能，旨在检测不完全选择性扫描，LRH和IHS，以及ALnLH。为了分析这些测试的性质，我们引入了一种新的计算方法，该方法可以模拟复杂的种群历史，包括迁移和变化的种群规模，以模拟受最近正选择影响的基因树。我们证明了IHS的表现远远好于其他两个统计量，对于最适合全基因组扫描的变异，在0.01水平上的幂高达0.74，对于最适合候选基因测试的变异，在0.01水平上的幂超过0.8。IHS统计的表现对复杂的人口历史和可变的重组率是稳健的。涉及其他两个统计数据的基因组扫描存在低功率和高假阳性率，ALn1H的错误发现率高达0.96%。IHS和ALnLH之间的性能差异并不是由于统计数据的性质造成的，而是因为缓解全基因组扫描中固有的多重比较问题的不同方法。我们介绍了一种新的方法来模拟受复杂人口统计情景下的积极选择影响的家谱。在基于该方法的功率分析中，IHS在检测不完全选择性扫描方面优于LRH和ALnLH。我们还表明，在候选基因测试中，单位点IHS统计量比多位点统计量更强大，但多位点统计量在应用于整个基因组扫描时保持了较低的错误发现率，并且只有很小的功率损失。我们的结果强调，在评估和解释全基因组扫描的阳性选择结果时，需要仔细考虑多重比较问题。
Though a variety of linkage disequilibrium tests have recently been introduced to measure the signal of recent positive selection, the statistical properties of the various methods have not been directly compared. While most applications of these tests have suggested that positive selection has played an important role in recent human history, the results of these tests have varied dramatically. Here, we evaluate the performance of three statistics designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To analyze the properties of these tests, we introduce a new computational method that can model complex population histories with migration and changing population sizes to simulate gene trees influenced by recent positive selection. We demonstrate that iHS performs substantially better than the other two statistics, with power of up to 0.74 at the 0.01 level for the variation best suited for full genome scans and a power of over 0.8 at the 0.01 level for the variation best suited for candidate gene tests. The performance of the iHS statistic was robust to complex demographic histories and variable recombination rates. Genome scans involving the other two statistics suffer from low power and high false positive rates, with false discovery rates of up to 0.96 for ALnLH. The difference in performance between iHS and ALnLH, did not result from the properties of the statistics, but instead from the different methods for mitigating the multiple comparison problem inherent in full genome scans. We introduce a new method for simulating genealogies influenced by positive selection with complex demographic scenarios. In a power analysis based on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective sweeps. We also show that the single-site iHS statistic is more powerful in a candidate gene test than the multi-site statistic, but that the multi-site statistic maintains a low false discovery rate with only a minor loss of power when applied to a scan of the entire genome. Our results highlight the need for careful consideration of multiple comparison problems when evaluating and interpreting the results of full genome scans for positive selection.
登录
查看更多内容
影响因子：
7
作者：
Pickrell, Joseph K.;Coop, Graham;Pritchard, Jonathan K.
通讯作者：
Pritchard, Jonathan K.
影响因子：
56.9
作者：
Hinds, DA;Stuve, LL;Cox, DR
通讯作者：
Cox, DR
在人类基因组中近期阳性选择的地图。
影响因子：
9.8
作者：
Voight BF;Kudaravalli S;Wen X;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
1.4
作者：
Coop, G;Griffiths, RC
通讯作者：
Griffiths, RC
影响因子：
7
作者：
Schaffner, SF;Foo, C;Altshuler, D
通讯作者：
Altshuler, D