Full title: A large‐scale transcriptome‐wide association study (TWAS) of 10 blood cell phenotypes reveals complexities of TWAS fine‐mapping

2021 ◽  
Author(s):  
Amanda L. Tapia ◽  
Bryce T. Rowland ◽  
Jonathan D. Rosen ◽  
Michael Preuss ◽  
Kris Young ◽  
...  
Keyword(s):  
Blood Cell ◽  
Association Study ◽  
Fine Mapping ◽  
Large Scale ◽  
Cell Phenotypes

scholarly journals The Polygenic and Monogenic Basis of Blood Traits and Diseases

2020 ◽  
Author(s):  
Dragana Vuckovic ◽  
Erik L. Bao ◽  
Parsa Akbari ◽  
Caleb A. Lareau ◽  
Abdou Mousas ◽  
...  
Keyword(s):  
Blood Cell ◽  
Genetic Variants ◽  
Gene Networks ◽  
Large Scale ◽  
European Ancestry ◽  
Mendelian Genetics ◽  
Physiological Processes ◽  
Clinical Disorders ◽  
Cell Phenotypes ◽  
Significant Health

SummaryBlood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including 563,946 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering the full allele frequency spectrum 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 cell traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell GWAS to interrogate clinically meaningful variants across the full allelic spectrum of human variation.

scholarly journals Trans-ancestry genome-wide association study identifies novel genetic mechanisms in rheumatoid arthritis

2021 ◽  
Author(s):  
Kazuyoshi Ishigaki ◽  
Saori Sakaue ◽  
Chikashi Terao ◽  
Yang Luo ◽  
Kyuto Sonehara ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Study ◽  
Fine Mapping ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genetic Research ◽  
Genome Wide Association ◽  
Polygenic Risk Score ◽  
Genome Wide

AbstractTrans-ancestry genetic research promises to improve power to detect genetic signals, fine-mapping resolution, and performances of polygenic risk score (PRS). We here present a large-scale genome-wide association study (GWAS) of rheumatoid arthritis (RA) which includes 276,020 samples of five ancestral groups. We conducted a trans-ancestry meta-analysis and identified 124 loci (P < 5 × 10-8), of which 34 were novel. Candidate genes at the novel loci suggested essential roles of the immune system (e.g., TNIP2 and TNFRSF11A) and joint tissues (e.g., WISP1) in RA etiology. Trans-ancestry fine mapping identified putatively causal variants with biological insights (e.g., LEF1). Moreover, PRS based on trans-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between European and East Asian populations. Our study provides multiple insights into the etiology of RA and improves genetic predictability of RA.

Development and study of a method for cell separation during white blood cell segmentation on images of bone marrow preparations in information and measurement systems for diagnostics of acute leukemia

2020 ◽  
pp. 68-72
Author(s):  
V.G. Nikitaev ◽  
A.N. Pronichev ◽  
V.V. Dmitrieva ◽  
E.V. Polyakov ◽  
A.D. Samsonova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Acute Leukemia ◽  
White Blood Cell ◽  
Cell Separation ◽  
Large Scale ◽  
Bone Marrow Cells ◽  
Automated Analysis ◽  
Cell Segmentation ◽  
Measurement Systems

The issues of using of information and measurement systems based on processing of digital images of microscopic preparations for solving large-scale tasks of automating the diagnosis of acute leukemia are considered. The high density of leukocyte cells in the preparation (hypercellularity) is a feature of microscopic images of bone marrow preparations. It causes the proximity of cells to eachother and their contact with the formation of conglomerates. Measuring of the characteristics of bone marrow cells in such conditions leads to unacceptable errors (more than 50%). The work is devoted to segmentation of contiguous cells in images of bone marrow preparations. A method of cell separation during white blood cell segmentation on images of bone marrow preparations under conditions of hypercellularity of the preparation has been developed. The peculiarity of the proposed method is the use of an approach to segmentation of cell images based on the watershed method with markers. Key stages of the method: the formation of initial markers and builds the lines of watershed, a threshold binarization, shading inside the outline. The parameters of the separation of contiguous cells are determined. The experiment confirmed the effectiveness of the proposed method. The relative segmentation error was 5 %. The use of the proposed method in information and measurement systems of computer microscopy for automated analysis of bone marrow preparations will help to improve the accuracy of diagnosis of acute leukemia.

scholarly journals On the effects of membrane viscosity on transient red blood cell dynamics

Soft Matter ◽  
2020 ◽  
Vol 16 (26) ◽  
pp. 6191-6205 ◽  
Author(s):  
Fabio Guglietta ◽  
Marek Behr ◽  
Luca Biferale ◽  
Giacomo Falcucci ◽  
Mauro Sbragaglia
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Blood Circulation ◽  
Hydraulic Properties ◽  
Large Scale ◽  
Mechanical Response ◽  
Cell Dynamics ◽  
Membrane Viscosity

Computational Fluid Dynamics is currently used to design and improve the hydraulic properties of biomedical devices, wherein the large scale blood circulation needs to be simulated by accounting for the mechanical response of RBCs at the mesoscale.

scholarly journals A Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e59035 ◽  
Author(s):  
Ruyang Zhang ◽  
Yang Zhao ◽  
Minjie Chu ◽  
Amar Mehta ◽  
Yongyue Wei ◽  
...  
Keyword(s):  
Lung Function ◽  
Association Study ◽  
Large Scale ◽  
Cotton Textile ◽  
Textile Workers ◽  
Endotoxin Exposure ◽  
Newly Hired
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