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

Evaluating the management of construction projects

SIGLEAvailable from British Library Document Supply Centre- DSC:DX182018 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Multicountry perspectives of relational contracting and integrated project teams

Worldwide calls for integration in construction translate into needs for relational alignment of both structural and operational arrangements, in order to successfully streamline the combined efforts of diverse interacting parties, for improved project delivery. Appropriate applications of relational contracting (RC) principles can help to achieve such integration. As such, the aims of the reported study are to examine the relative usefulness of various potential factors and strategies and to offer suitable contractual and noncontractual incentives, for building an RC culture and building integrated project teams (IPTs) in construction. Results from statistical analyses of 224 questionnaire responses from five countries are presented. Trust and trust-based operational arrangements are seen to effectively offer the required incentives for implementing various RC-based arrangements in construction where top management commitment and their support play a vital role. The choices of country-specific approaches suggest various patterns of integration through project-based partnering type RC, e.g.,cliental initiative and removing client related barriers in Hong Kong, removing uncongenial organizational and/or system-based barriers from the client's side in Australia, teamworking by cliental initiatives through contractual arrangements in The Netherlands, removing organizational and/or system-based barriers in the U.K., importance of trust and communication-related factors in Singapore, with no specific strategy in this respect. The outcomes also suggest the need for a highly interrelated and consolidated approach for spreading RC. Outcomes of this study are expected to benefit both industry practitioners and researchers in exploring, designing, and implementing various RC-based working arrangements. © 2012 American Society of Civil Engineers.link_to_subscribed_fulltex

Building a relational contracting culture and integrated teams

10.1139/L06-119Canadian Journal of Civil Engineering34175-88CJCE

Reconstructing cultures for relational contracting

10.1061/(ASCE)0733-9364(2005)131:10(1065)Journal of Construction Engineering and Management131101065-1075JCEM

Constructing relationally integrated teams

10.1061/(ASCE)0733-9364(2005)131:10(1076)Journal of Construction Engineering and Management131101076-1086JCEM

Targeting relationally integrated teams for sustainable PPPS

10.1108/09699980710829030Engineering, Construction and Architectural Management146581-59