44 research outputs found
Lithogeochemistry of the meta-igneous units from Arroio Grande Ophiolitic Complex, southernmost Brazil
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
Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations
Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach
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The Design of a Pulsed Homopolar Generator Power Supply for a High Current Laboratory
Center for Electromechanic
Ganderia-Laurentia collision in the Caledonides of Great Britain and Ireland
During terrane convergence, an influx of clastic sediment from an upper plate onto a lower plate is an early indication of terrane juxtaposition. In the Caledonides of Great Britain and Ireland, units accreted to Laurentia during the early Palaeozoic Era include peri-Gondwanan terrane assemblages that earlier separated from West Gondwana. However, the Southern Uplands Terrane contains detrital zircon populations apparently derived entirely from Laurentia, characterized by a large, asymmetric Mesoproterozoic peak and a scarcity of zircon at 600 Ma and 2.1 Ga. In contrast, Cambrian and Ordovician rocks from the Lake District and the Leinster Massif of Ireland show abundant grains with these ages, together with a range of Mesoproterozoic zircon. These characteristics are shared with the Monian terrane of Anglesey and with Ganderia in the Appalachians, indicating probable derivation from Amazonia in West Gondwana. Silurian sandstones from the Lake District show an influx of Laurentia-derived zircon, and lack the peri-Gondwanan signal. This indicates that in the Caledonides, Ganderia was not accreted to the Laurentian margin until c. 430 Ma, in contrast to the Ordovician accretion of Ganderian fragments recorded in the Appalachians, suggesting that the configuration of the closing Iapetus Ocean varied significantly along the strike of the orogen