How effectively can HIV phylogenies be used to measure heritability?
How effectively can HIV phylogenies be used to measure heritability?
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DOI：
10.1093/emph/eot019
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发表时间：
2013-01
期刊：
影响因子：
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通讯作者：
Fraser C
中科院分区：
文献类型：
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作者：
Shirreff G;Alizon S;Cori A;Günthard HF;Laeyendecker O;van Sighem A;Bezemer D;Fraser C
背景和目的：HIV-1感染的严重程度，通过设定点病毒载量（SPVL）测量，个体之间差异很大。它在感染之间的遗传性量化了病原体基因型对疾病严重程度的控制。遗传力估计在研究之间差异很大，但方法的差异使比较变得困难。系统发育比较分析提供了系统发育信号的措施，但目前还不清楚如何解释它们的变异在SPVL的病毒基因型控制的分数方面。方法学：我们提出的计算方法，链接统计总结系统发育信号的遗传力，H2，以测试和量化它。我们重新分析来自瑞士和乌干达的数据，并将其应用到新的数据来自荷兰。我们系统地比较建立和新的（如系统发育对，PP）系统发育信号统计。结果：遗传力估计值因方法和数据集而异。几种方法始终能够检测到模拟遗传力以上，但没有低于。Pagel的λ是最稳健和敏感的。PP方法在荷兰的数据中没有发现遗传力，而Pagel的λ仅在一个狭窄的细分中发现了显著的遗传力（P =0.038）。遗传力估计为h2=0.52（95%置信区间0.00-0.63）。结论和影响：这个标准化的措施，H2，允许队列之间的遗传可比性。我们证实了瑞士数据中的高遗传性，但在乌干达和荷兰的数据中都没有，在那里几乎没有显著性或无法检测到。现有的系统发育方法不适合检测下面的遗传性，这可能是生物学上重要的。
Background and objectives: The severity of HIV-1 infection, measured by set-point viral load (SPVL), is highly variable between individuals. Its heritability between infections quantifies the control the pathogen genotype has over disease severity. Heritability estimates vary widely between studies, but differences in methods make comparison difficult. Phylogenetic comparative analysis offers measures of phylogenetic signal, but it is unclear how to interpret them in terms of the fraction of variance in SPVL controlled by the virus genotype. Methodology: We present computational methods which link statistics summarizing phylogenetic signal to heritability, h2 in order to test for and quantify it. We re-analyse data from Switzerland and Uganda, and apply it to new data from the Netherlands. We systematically compare established and new (e.g. phylogenetic pairs, PP) phylogenetic signal statistics. Results: Heritability estimates varied by method and dataset. Several methods were consistently able to detect simulated heritability above , but none below. Pagel’s λ was the most robust and sensitive. The PP method found no heritability in the Netherlands data, whereas Pagel’s λ found significant heritability only in a narrow subdivision (P =0.038). Heritability was estimated at h2=0.52 (95% confidence interval 0.00–0.63). Conclusions and implications: This standardized measure, h2, allows comparability of heritability between cohorts. We confirm high heritability in Swiss data, but neither in Ugandan data nor in the Netherlands, where it is barely significant or undetectable. Existing phylogenetic methods are ill-suited for detecting heritability below , which may nonetheless be biologically important.