Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.</p

A Survey on 3D Virtual Object Manipulation: From the Desktop to Immersive Virtual Environments

Interactions within virtual environments often require manipulating 3D virtual objects. To this end, researchers have endeavoured to find efficient solutions using either traditional input devices or focusing on different input modalities, such as touch and mid\u2010air gestures. Different virtual environments and diverse input modalities present specific issues to control object position, orientation and scaling: traditional mouse input, for example, presents non\u2010trivial challenges because of the need to map between 2D input and 3D actions. While interactive surfaces enable more natural approaches, they still require smart mappings. Mid\u2010air gestures can be exploited to offer natural manipulations mimicking interactions with physical objects. However, these approaches often lack precision and control. All these issues and many others have been addressed in a large body of work. In this article, we survey the state\u2010of\u2010the\u2010art in 3D object manipulation, ranging from traditional desktop approaches to touch and mid\u2010air interfaces, to interact in diverse virtual environments. We propose a new taxonomy to better classify manipulation properties. Using our taxonomy, we discuss the techniques presented in the surveyed literature, highlighting trends, guidelines and open challenges, that can be useful both to future research and to developers of 3D user interfaces

Let’s jam the reactable: peer learning during musical improvisation with a tabletop tangible interface

There has been little research on how interactions with tabletop and Tangible User Interfaces (TUIs) by groups of users change over time. In this article, we investigate the challenges and opportunities of a tabletop tangible interface based on constructive building blocks. We describe a long-term lab study of groups of expert musicians improvising with the Reactable, a commercial tabletop TUI for music performance. We examine interaction, focusing on interface, tangible, musical, and social phenomena. Our findings reveal a practice-based learning between peers in situated contexts, and new forms of participation, all of which is facilitated by the Reactable's tangible interface, if compared to traditional musical ensembles. We summarise our findings as a set of design considerations and conclude that construction processes on interactive tabletops support learning by doing and peer learning, which can inform constructivist approaches to learning with technology