ADHD: Sibling interaction or dominance: An evaluation of statistical power

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

A twin study of differentiation of cognitive abilities in childhood

INTRODUCTION The structure of individual differences in cognitive abilities during development has received considerable attention in cognitive developmental theory (Schaie, 1994; Vernon, 1976). One important hypothesis, dating back to Garrett (1946; see also Carroll, 1993; Reinert, 1970; Wohlwill, 1973), states that cognitive abilities become increasingly more differentiated during development. In operational terms, this means that the intercorrelations among psychometric measures of ability decrease during normal cognitive development in children. So far, support for this hypothesis has been poor. In an early review of about 60 factor analytic studies, Reinert (1970) suggested that a trend toward increased differentiation was present. However, this conclusion was based on the selection of studies that actually reported a change. In a more recent review, Carroll (1993) failed to find clear evidence for the differentiation of abilities. More recent cross-sectional studies of the ch

A methodology for automated feature engineering in training of shallow neural networks for prediction of multi-linear growth failures (“Nova Algorithm”)

Deep learning requires a large data set. When working with smaller data sets we need an automated approach for feature learning as a pre-processing step to create the training set for a shallow neural network with one hidden layer. The outcome of the neural net classifier is filtered using post-processing rules over a defined wait and quiet period to create an ensemble prediction with higher quality. This gives us the benefits of deep learning, but with a smaller data set. A partial implementation of this methodology was used for a pilot release for prediction of Common Previsioning Group (CPG) growth failures in 3PAR storage devices, using a trained neural net model with additional derived attributes, pre-processing rules and post-processing steps, applied to 90 days history of logical disk free space for each CPG on the storage device

Power calculations using exact data simulation: A useful tool for genetic study designs.

Statistical power calculations constitute an essential first step in the planning of scientific studies. If sufficient summary statistics are available, power calculations are in principle straightforward and computationally light. In designs, which comprise distinct groups (e.g., MZ & DZ twins), sufficient statistics can be calculated within each group, and analyzed in a multi-group model. However, when the number of possible groups is prohibitively large (say, in the hundreds), power calculations on the basis of the summary statistics become impractical. In that case, researchers may resort to Monte Carlo based power studies, which involve the simulation of hundreds or thousands of replicate samples for each specified set of population parameters. Here we present exact data simulation as a third method of power calculation. Exact data simulation involves a transformation of raw data so that the data fit the hypothesized model exactly. As in power calculation with summary statistics, exact data simulation is computationally light, while the number of groups in the analysis has little bearing on the practicality of the method. The method is applied to three genetic designs for illustrative purposes

Do Interventions Designed to Support Shared Decision-Making Reduce Health Inequalities? : A Systematic Review and Meta-Analysis

Copyright: © 2014 Durand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Increasing patient engagement in healthcare has become a health policy priority. However, there has been concern that promoting supported shared decision-making could increase health inequalities. Objective: To evaluate the impact of SDM interventions on disadvantaged groups and health inequalities. Design: Systematic review and meta-analysis of randomised controlled trials and observational studies.Peer reviewe

Assessment and Etiology of Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder in Boys and Girls

Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are more common in boys than girls. In this paper, we investigated whether the prevalence differences are attributable to measurement bias. In addition, we examined sex differences in the genetic and environmental influences on variation in these behaviors. Teachers completed the Conners Teacher Rating Scale-Revised:Short version (CTRS-R:S) in a sample of 800 male and 851 female 7-year-old Dutch twins. No sex differences in the factor structure of the CTRS-R:S were found, implying the absence of measurement bias. The heritabilities for both ADHD and ODD were high and were the same in boys and girls. However, partly different genes are expressed in boys and girls

PfRH5: A Novel Reticulocyte-Binding Family Homolog of Plasmodium falciparum that Binds to the Erythrocyte, and an Investigation of Its Receptor

Multiple interactions between parasite ligands and their receptors on the human erythrocyte are a condition of successful Plasmodium falciparum invasion. The identification and characterization of these receptors presents a major challenge in the effort to understand the mechanism of invasion and to develop the means to prevent it. We describe here a novel member of the reticulocyte-binding family homolog (RH) of P. falciparum, PfRH5, and show that it binds to a previously unrecognized receptor on the RBC. PfRH5 is expressed as a 63 kDa protein and localized at the apical end of the invasive merozoite. We have expressed a fragment of PfRH5 which contains the RBC-binding domain and exhibits the same pattern of interactions with the RBC as the parent protein. Attachment is inhibited if the target cells are exposed to high concentrations of trypsin, but not to lower concentrations or to chymotrypsin or neuraminidase. We have determined the affinity, copy number and apparent molecular mass of the receptor protein. Thus, we have shown that PfRH5 is a novel erythrocyte-binding ligand and the identification and partial characterization of the new RBC receptor may indicate the existence of an unrecognized P. falciparum invasion pathwa

Are preferences over health states informed?

BACKGROUND: The use of preference-elicitation tasks for valuing health states is well established, but little is known about whether these preferences are informed. Preferences may not be informed because individuals with little experience of ill health are asked to value health states. The use of uninformed preferences in cost-effectiveness can result in sub-optimal resource allocation. The aim of this study was to pilot a novel method to assess whether members of the public are informed about health states they value in preference-elicitation tasks. METHODS: The general public was said to be informed if the expectations of the public about the effect of ill health on people's lives were in agreement with the experience of patients. Sixty-two members of the public provided their expectations of the consequences of ill health on five life domains (activities, enjoyment, independence, relationships, and avoiding being a burden). A secondary dataset was used to measure patient experience on those five consequences. RESULTS: There were differences between the expectations of the public and the experience of patients. For example, for all five life consequences the public underestimated the effects of problems in usual activities compared to problems in mobility. They also underestimated the effect of 'anxiety or depression' compared to physical problems on enjoyment of life and on the quality of personal relationships. CONCLUSIONS: This proof-of-concept study showed that it is possible to test whether preferences are informed. This study should be replicated using a larger sample. The findings suggest that preferences over health states in this sample are not fully informed because the participants do not have accurate expectations about the consequences of ill health. These uninformed preferences may not be adequate for allocation of public resources, and research is needed into methods to make them better informed