The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Flexible delivery approaches to couple relationship education: predictors of initial engagement and retention of couples

In this study, using a national recruitment strategy, we tested the different factors that influence retention in four different types of relationship education (RE), a self-directed book, assessment and feedback, and a six session Couple CARE program delivered by email or by phone. Of all the factors considered, required program effort, highly valuing marriage, religiosity, education, and step-family status were able to predict with seventy percent accuracy which couples would complete or not complete their RE experience. Program effort was substantially better at predicting retention than all other variables. Retention was high in the book and assessment conditions but was much lower in the two Couple CARE conditions where more effort and time was required. Initial engagement was higher in the email based Couple CARE condition but overall retention was higher in the phone based condition. Important implications for current and future RE efforts are proposed