Rietveld M J H, Posthuma l D, Dolan C V, Boomsma D I
Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Behav Genet. 2003 May;33(3):247-55. doi: 10.1023/a:1023490307170.
Sibling interaction effects are suggested by a difference in phenotypic variance between monozygotic (MZ) twins and dizygotic (DZ) twins, and a pattern of twin correlations that is inconsistent with additive genetic influences. Notably, negative sibling interaction will result in MZ correlations which are more than twice as high as DZ correlations, a pattern also seen in the presence of genetic dominance. Negative sibling interaction effects have been reported in most genetic studies on Attention Deficit Hyperactivity Disorder (ADHD) and related phenotypes, while the presence of genetic dominance is not always considered in these studies. In the present paper the statistical power to detect both negative sibling interaction effects and genetic dominance is explored. Power calculations are presented for univariate models including sources of variation due to additive genetic influences, unique environmental influences, dominant genetic influences and a negative sibling interaction (i.e., contrast effect) between phenotypes of twins. Parameter values for heritability and contrast effects are chosen in accordance with published behavior genetic studies on ADHD and associated phenotypes. Results show that when both genetic dominance and contrast effects are truly present and using a classical twin design, genetic dominance is more likely to go undetected than the contrast effect. Failure to detect the presence of genetic dominance consequently gives rise to slightly biased estimates of additive genetic effects, unique environmental effects, and the contrast effect. Contrast effects are more easily detected in the absence of genetic dominance. If the significance of the contrast effect is evaluated while also including genetic dominance, small contrast effects are likely to go undetected, resulting in a relatively large bias in estimates of the other parameters. Alternative genetic designs, such as adding pairs of unrelated siblings reared together to a classical twin design, or adding non-twin siblings to twin pairs, greatly enhances the statistical power to detect contrast effects as well as the power to distinguish between genetic dominance and contrast effects.
同卵双胞胎（MZ）和异卵双胞胎（DZ）之间表型方差的差异以及与加性遗传影响不一致的双胞胎相关性模式表明存在同胞相互作用效应。值得注意的是，负面的同胞相互作用会导致同卵双胞胎的相关性比异卵双胞胎的相关性高出两倍以上，这种模式在存在遗传显性的情况下也会出现。在大多数关于注意力缺陷多动障碍（ADHD）及相关表型的遗传研究中都报告了负面的同胞相互作用效应，而这些研究中并不总是考虑遗传显性的存在。在本文中，探讨了检测负面同胞相互作用效应和遗传显性的统计功效。给出了单变量模型的功效计算，该模型包括由于加性遗传影响、独特环境影响、显性遗传影响以及双胞胎表型之间的负面同胞相互作用（即对比效应）引起的变异来源。遗传力和对比效应的参数值是根据已发表的关于ADHD及相关表型的行为遗传学研究来选择的。结果表明，当遗传显性和对比效应都确实存在且使用经典双胞胎设计时，遗传显性比对比效应更有可能未被检测到。未能检测到遗传显性的存在会导致对加性遗传效应、独特环境效应和对比效应的估计略有偏差。在不存在遗传显性的情况下，对比效应更容易被检测到。如果在评估对比效应的显著性时也包括遗传显性，小的对比效应很可能未被检测到，从而导致其他参数估计中的相对较大偏差。替代的遗传设计，例如在经典双胞胎设计中加入一起抚养的无关同胞对，或者在双胞胎对中加入非双胞胎同胞，大大提高了检测对比效应的统计功效以及区分遗传显性和对比效应的能力。
