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

Structural analysis of health-relevant policy-making information exchange networks in Canada

Abstract Background Health systems worldwide struggle to identify, adopt, and implement in a timely and system-wide manner the best—evidence-informed—policy-level practices. Yet, there is still only limited evidence about individual and institutional best practices for fostering the use of scientific evidence in policy-making processes The present project is the first national-level attempt to (1) map and structurally analyze—quantitatively—health-relevant policy-making networks that connect evidence production, synthesis, interpretation, and use; (2) qualitatively investigate the interaction patterns of a subsample of actors with high centrality metrics within these networks to develop an in-depth understanding of evidence circulation processes; and (3) combine these findings in order to assess a policy network’s “absorptive capacity” regarding scientific evidence and integrate them into a conceptually sound and empirically grounded framework. Methods The project is divided into two research components. The first component is based on quantitative analysis of ties (relationships) that link nodes (participants) in a network. Network data will be collected through a multi-step snowball sampling strategy. Data will be analyzed structurally using social network mapping and analysis methods. The second component is based on qualitative interviews with a subsample of the Web survey participants having central, bridging, or atypical positions in the network. Interviews will focus on the process through which evidence circulates and enters practice. Results from both components will then be integrated through an assessment of the network’s and subnetwork’s effectiveness in identifying, capturing, interpreting, sharing, reframing, and recodifying scientific evidence in policy-making processes. Discussion Knowledge developed from this project has the potential both to strengthen the scientific understanding of how policy-level knowledge transfer and exchange functions and to provide significantly improved advice on how to ensure evidence plays a more prominent role in public policies