Parsa Akbari
A5086602447- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Blood groups and transfusion
- Platelet Disorders and Treatments
- Hemoglobinopathies and Related Disorders
- Asthma and respiratory diseases
- Metabolism, Diabetes, and Cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- BRCA gene mutations in cancer
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genetic Syndromes and Imprinting
- Eosinophilic Disorders and Syndromes
- Genetic and phenotypic traits in livestock
- Cancer-related molecular mechanisms research
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Cell Function and Interaction
- Lipid metabolism and disorders
- Cardiovascular Disease and Adiposity
- Venous Thromboembolism Diagnosis and Management
- Renal Diseases and Glomerulopathies
- Antiplatelet Therapy and Cardiovascular Diseases
- PARP inhibition in cancer therapy
- Nonmelanoma Skin Cancer Studies
Regeneron (United States)
2021-2025
University of Cambridge
2020-2024
British Heart Foundation
2020-2023
Medical Research Council
2020-2022
Wellcome Sanger Institute
2020-2022
Genomics (United Kingdom)
2020-2022
MRC Biostatistics Unit
2020-2022
National Institute for Health Research
2020-2022
How genes affect human obesity Obesity is linked to many diseases, including diabetes, cancer, and heart disease. There thus great interest in understanding how predispose individuals to, or protect from, obesity. Akbari et al. sequenced more than 600,000 exomes from the United Kingdom, States, Mexico identified 16 rare coding variants (see Perspective by Yeo O'Rahilly). Some of alleles associated with body mass index (BMI) were brain-expressed G protein–coupled receptors. One variant allele...
Exome sequencing in hundreds of thousands persons may enable the identification rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for discovery new therapeutic targets.
Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with at exome-wide significance. We show 6-fold larger effect fat-distribution rare coding variants compared fine-mapped common alleles, enrichment expressed adipose tissue causal partial lipodystrophies, evidence sex-dimorphism....
Abstract Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and find novel contributors human disease. We used gene-based collapsing tests genes associated with glucose, HbA1c type 2 diabetes (T2D) diagnosis in 379,066 exome-sequenced participants the UK Biobank. identified associations for GCK, HNF1A PDX1 , which are known be involved Mendelian forms diabetes. Notably, we uncovered GIGYF1 a gene not previously implicated by genetics predicted...
Genetic association studies for blood cell traits, which are key indicators of health and immune function, have identified several hundred associations defined a complex polygenic architecture. Polygenic scores (PGSs) traits potential clinical utility in disease risk prediction prevention, but designing PGS remains challenging the optimal methods unclear. To address this, we evaluated relative performance 6 to develop 26 including standard method pruning thresholding (P + T) 5 learning...
Abstract Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes—including cell-type specific measures granularity, nucleic acid content reactivity—in 41,515 participants the INTERVAL study. identify 2172 distinct variant-trait...
Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads changes in platelet characteristics, thereby increasing thrombotic risk. The effect of on traits (measured by Sysmex) was explored 33 388 UK blood donors (INTERVAL study). Linear regression showed positively associated with greater plateletcrit (PCT), count (PLT), immature (IPC), and side...
The process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood count. Proplatelet formation releases into bloodstream beads-on-a-string preplatelets, which undergo fission mature platelets. For first time, we show that preplatelet is third, tightly regulated, critical akin cytokinesis regulates We deficiency in cytokine...
Abstract Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and find novel contributors human disease. We used gene-based collapsing tests genes associated with glucose, HbA1c type 2 diabetes (T2D) diagnosis in 363,977 exome-sequenced participants the UK Biobank. identified associations for GCK, HNF1A PDX1 , which are known be involved Mendelian forms diabetes. Notably, we uncovered GIGYF1 a gene not previously implicated by genetics, predicted...
SUMMARY Thousands of genetic associations with phenotypes blood cells are known, but few relevant to cell function. We performed GWAS 63 flow-cytometry phenotypes, including measures granularity, nucleic acid content, and reactivity, in 39,656 participants the INTERVAL study, identifying 2,172 variant-trait associations. These include mediated by functional cellular structures such as secretory granules, implicated vascular, thrombotic, inflammatory neoplastic diseases. By integrating our...
Abstract Polygenic scores (PGSs) for blood cell traits can be constructed using summary statistics from genome-wide association studies. As the selection of variants and modelling their interactions in PGSs may limited by univariate analysis, therefore, such a conventional method yield sub-optional performance. This study evaluated relative effectiveness four machine learning deep methods, as well method, construction 26 traits, data UK Biobank (n=~400,000) INTERVAL (n=~40,000). Our results...
SUMMARY Most loci identified by GWAS have been found in populations of European ancestry (EA). In trans-ethnic meta-analyses for 15 hematological traits 746,667 participants, including 184,535 non-EA individuals, we 5,552 trait-variant associations at P <5×10 −9 , 71 novel not EA populations. We also ancestry-specific variants EA, an IL7 missense variant South Asians associated with lymphocyte count vivo and secretion levels vitro . Fine-mapping prioritized annotated as functional,...
Summary Blood 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 large-scale international collaborative effort, including 563,946 European ancestry participants, discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering the full allele frequency spectrum of variation impacting...
Neutrophils are essential immune cells loaded with cytosolic granules that contain potent antimicrobial and immunostimulatory molecules. Since alterations of neutrophil granule contents associated both immunodeficiency hyperinflammation, identification regulators can aid in understanding neutrophil-driven pathologies. Here we perform a systematic prioritisation genetic variants cytometric side scatter (SSC), proxy for granularity, identified genome wide association study (GWAS) blood...
Few genome-wide association studies (GWAS) analyzing genetic regulation of morphological traits white blood cells have been reported. We carried out a GWAS 12 in 869 individuals from the general population Sardinia, Italy. These traits, included measures cell volume, conductivity and light scatter four white-cell populations (eosinophils, lymphocytes, monocytes, neutrophils). This analysis yielded seven statistically significant signals, which were novel (four novel, PRG2, P2RX3, two CDK6)....
Abstract A higher body mass index (BMI) is a recognised risk factor for thrombosis. Platelets are essential haemostasis but also contribute to thrombosis when activated pathologically. We hypothesised that an increase in BMI may lead changes platelet characteristics, thereby contributing increased thrombotic risk. The effect of on traits measured by Sysmex XN-1000 was explored 33388 UK blood donors from the INTERVAL study. Linear regression used observational analyses between and...
Melanoma is the most common form of skin cancer, and disease image segmentation plays a vital role in automated diagnosis cancer. A primary challenge other object recognition techniques large amount redundant input information which often obfuscates critical features. In context dermatoscopy lesion we show that unsupervised clustering algorithms applied to images can reduce local redundancy result dramatic improvements performance. Our work proposes algorithm combining an simple linear...
In this analysis, we studied the use of Mendelian randomization to identify risk factors coronary artery disease (CAD), a major cause cardiovascular disease. Identifying CAD are critical understanding and managing Our analysis combined results from 28 genetic analyses 12 unique studies. For each variation, obtained variant ID, chromosome, base-pair position, reference alternative alleles estimated effect p-value variation on outcome. We hypothesized that traits which correlated with outcomes...
Images from closed-circuit television (CCTV) cameras are often stored with poor resolution due to technical and data storage limitations, reducing the utility of these images. In this study, we propose that informed design training an enhanced deep residual network (EDSR) can increase CCTV This work is first published application EDSR methodology for increasing image resolution. We utilized a dataset 986 images trained tested generating high-resolution low-resolution dataset. Implementing...