Christian J C, Norton J A, Sorbel J, Williams C J
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202-5251, USA.
Genet Epidemiol. 1995;12(1):27-35. doi: 10.1002/gepi.1370120104.
In order to investigate currently used model fitting strategies for twin data, analysis of variance (ANOVA) and path-maximum-likelihood (PATH-ML) methods of analyzing twin data were compared using simulation studies of 50 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs. Phenotypic covariance was partitioned into additive genetic effects (A), environmental effects common to cotwins (C), and environmental variance unique to individuals (E). ANOVA and PATH-ML had identical power to detect total covariance. The PATH-ML AE model was much more powerful than ANOVA comparisons of rMZ and rDZ to detect A. However, to be unbiased, the AE model requires the assumption that C = 0.0. To allow use of the AE model to estimate A, the null hypothesis C = 0.0 is tested by comparing the goodness of fit of the ACE and AE models. Simulation of 50 MZ and 50 DZ pairs revealed that C must be greater than 55% of total variance before the null hypothesis would be rejected (P < 0.05) 80% of the time. Several recent publications were reviewed in which the null hypothesis C = 0.0 was accepted and apparently upwardly biased estimates of A, containing C, were presented with unrealistic P values. It was concluded that use of the AE model to estimate A gives an inflated view of the power of relatively small twin studies. It was recommended that ANOVA or comparison of the ACE and CE PATH-ML models be used to estimate and test the significance of A as neither requires that C = 0.0.
为了研究当前用于双胞胎数据的模型拟合策略,通过对50对同卵双胞胎(MZ)和50对异卵双胞胎(DZ)进行模拟研究,比较了分析双胞胎数据的方差分析(ANOVA)和路径最大似然法(PATH-ML)。表型协方差被分解为加性遗传效应(A)、双胞胎共同的环境效应(C)和个体特有的环境方差(E)。ANOVA和PATH-ML在检测总协方差方面具有相同的功效。PATH-ML AE模型在检测A方面比rMZ和rDZ的ANOVA比较更具功效。然而,为了无偏,AE模型需要假设C = 0.0。为了使用AE模型估计A,通过比较ACE和AE模型的拟合优度来检验零假设C = 0.0。对50对MZ和50对DZ双胞胎的模拟显示,在零假设被拒绝(P < 0.05)80%的时间之前,C必须大于总方差的55%。回顾了最近的几篇出版物,其中零假设C = 0.0被接受,并且出现了包含C的明显向上偏差的A估计值以及不切实际的P值。得出的结论是,使用AE模型估计A会高估相对较小双胞胎研究的功效。建议使用ANOVA或ACE和CE PATH-ML模型的比较来估计和检验A的显著性,因为这两种方法都不需要C = 0.0。