ADHD: sibling interaction or dominance: an evaluation of statistical power

Sibling interaction effects are suggested by a difference in phenotypic variance between mono-zygotic (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.