Kleensang A, Franke D, Alcaïs A, Abel L, Müller-Myhsok B, Ziegler A
Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, DE-23538 Lübeck, Germany.
Hum Hered. 2010;69(3):202-11. doi: 10.1159/000289596. Epub 2010 Mar 5.
The choices of study design and statistical approach for mapping a quantitative trait (QT) are of great importance. Larger sibships and a study design based upon phenotypically extreme siblings can be expected to have a greater statistical power. On the other hand, selected samples and/or deviation from normality can influence the robustness and power. Unfortunately, the effects of violation of multivariate normality assumptions and/or selected samples are only known for a limited number of methods. Some recommendations are available in the literature, but an extensive comparison of robustness and power under several different conditions is lacking.
We compared eight freely available and commonly applied QT mapping methods in a Monte-Carlo simulation study under 36 different models and study designs (three genetic models, three selection schemes, two family structures and the possible effect of deviation from normality).
Empirical type I error fractions and empirical power are presented and explained as a whole and for each method separately, followed by a thorough discussion.
The results from this extensive comparison could serve as a valuable source for the choice of the study design and the statistical approach for mapping a QT.
对于定量性状(QT)定位而言,研究设计和统计方法的选择至关重要。预计更大的同胞对样本以及基于表型极端同胞的研究设计会具有更强的统计效力。另一方面,选择样本和/或偏离正态性会影响稳健性和效力。遗憾的是,对于有限数量的方法,违反多元正态性假设和/或选择样本的影响仅为已知。文献中有一些建议,但缺乏在几种不同条件下对稳健性和效力的广泛比较。
在蒙特卡洛模拟研究中,我们在36种不同模型和研究设计(三种遗传模型、三种选择方案、两种家系结构以及偏离正态性的可能影响)下比较了八种免费可得且常用的QT定位方法。
给出并整体及分别针对每种方法解释了经验性I类错误率和经验性效力,随后进行了深入讨论。
这一广泛比较的结果可为QT定位研究设计和统计方法的选择提供有价值的参考。