scholarly journals Influence of Genetic Variants in EGF and Other Genes on Hematological Traits in Korean Populations by a Genome-Wide Approach

2015 ◽  
Vol 2015 ◽  
pp. 1-9
Author(s):  
Yun Kyoung Kim ◽  
Ji Hee Oh ◽  
Young Jin Kim ◽  
Mi Yeong Hwang ◽  
Sanghoon Moon ◽  
...  
Keyword(s):  
Platelet Count ◽  
Blood Cell ◽  
Cell Count ◽  
Ethnic Groups ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Blood Cell Count ◽  
Genetic Loci ◽  
Genome Wide ◽  
A Genome

Hematological traits are important health indicators and are used as diagnostic clinical parameters for human disorders. Recently, genome-wide association studies (GWAS) identified many genetic loci associated with hematological traits in diverse ethnic groups. However, additional GWAS are necessary to elucidate the breadth of genetic variation and the underlying genetic architecture represented by hematological metrics. To identify additional genetic loci influencing hematological traits (such as hematocrit, hemoglobin concentration, white blood cell count, red blood cell count, and platelet count), we conducted GWAS and meta-analyses on data from 12,509 Korean individuals grouped into population-based cohorts. Of interest is EGF, a factor plays a role in the proliferation and differentiation of hematopoietic progenitor cells. We identified a novel EGF variant, which associated with platelet count in our study (Pcombined=2.44×10-15). Our study also replicated 16 genetic associations related to five hematological traits with genome-wide significance (P<5×10-8) that were previously established in other ethnic groups. Of these, variants influencing platelet count are distributed across several genes and have pleiotropic effects in coronary artery disease and dyslipidemia. Our findings may aid in elucidating molecular mechanisms underlying not only hematopoiesis but also inflammatory and cardiovascular diseases.

scholarly journals Identification of nine novel loci related to hematological traits in a Japanese population

2018 ◽  
Vol 50 (9) ◽  
pp. 758-769 ◽  
Author(s):  
Yoshiki Yasukochi ◽  
Jun Sakuma ◽  
Ichiro Takeuchi ◽  
Kimihiko Kato ◽  
Mitsutoshi Oguri ◽  
...  
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
Genetic Variants ◽  
Association Studies ◽  
Single Point ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Monocyte Count ◽  
Blood Cell Count ◽  
Genome Wide

Recent genome-wide association studies have identified various genetic variants associated with hematological traits. Although it is possible that quantitative data of hematological traits are varied among the years examined, conventional genome-wide association studies have been conducted in a cross-sectional manner that measures traits at a single point in time. To address this issue, we have traced blood profiles in 4,884 Japanese individuals who underwent annual health check-ups for several years. In the present study, longitudinal exome-wide association studies were conducted to identify genetic variants related to 13 hematological phenotypes. The generalized estimating equation model showed that a total of 67 single nucleotide polymorphisms (SNPs) were significantly [false discovery rate (FDR) of <0.01] associated with hematological phenotypes. Of the 67 SNPs, nine SNPs were identified as novel hematological markers: rs4686683 of SENP2 for red blood cell count (FDR = 0.008, P = 5.5 × 10−6); rs3917688 of SELP for mean corpuscular volume (FDR = 0.005, P = 2.4 × 10−6); rs3133745 of C8orf37-AS1 for white blood cell count (FDR = 0.003, P = 1.3 × 10−6); rs13121954 at 4q31.2 for basophil count (FDR = 0.007, P = 3.1 × 10−5); rs7584099 at 2q22.3 (FDR = 2.6 × 10−5, P = 8.8 × 10−8), rs1579219 of HCG17 (FDR = 0.003, P = 2.0 × 10−5), and rs10757049 of DENND4C (FDR = 0.008, P = 5.6 × 10−5) for eosinophil count; rs12338 of CTSB for neutrophil count (FDR = 0.007, P = 2.9 × 10−5); and rs395967 of OSMR-AS1 for monocyte count (FDR = 0.008, P = 3.2 × 10−5).

scholarly journals White Blood Cells and Severe COVID-19: A Mendelian Randomization Study

2021 ◽  
Vol 11 (3) ◽  
pp. 195
Author(s):  
Yitang Sun ◽  
Jingqi Zhou ◽  
Kaixiong Ye
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Blood Cells ◽  
Mendelian Randomization ◽  
Association Studies ◽  
White Blood Cells ◽  
Genome Wide Association Studies ◽  
Blood Cell Count

Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60–0.95), 0.70 (95% CI: 0.54–0.92), and 0.85 (95% CI: 0.73–0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy.

scholarly journals Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daniel L. McCartney ◽  
Josine L. Min ◽  
Rebecca C. Richmond ◽  
Ake T. Lu ◽  
Maria K. Sobczyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Biological Aging ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Biomarkers Of Aging ◽  
Genome Wide ◽  
Shared Genetic

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

scholarly journals The Genetic Basis of Hypertriglyceridemia

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Germán D. Carrasquilla ◽  
Malene Revsbech Christiansen ◽  
Tuomas O. Kilpeläinen
Keyword(s):  
Genetic Basis ◽  
Association Studies ◽  
Cumulative Effect ◽  
Genome Wide Association Studies ◽  
Genetic Loci ◽  
Risk Variants ◽  
Genome Wide ◽  
Severe Hypertriglyceridemia ◽  
Increased Risk ◽  
Polygenic Scores

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.

scholarly journals Enoxaparin-induced reactive thrombocytosis: a case report

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tao Xiang ◽  
Ming Cheng
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Hip Replacement ◽  
Low Molecular Weight ◽  
Blood Cell Count ◽  
Reactive Thrombocytosis

Abstract Background Enoxaparin is an anticoagulant that falls in the class of medications called low molecular weight heparins (LMWHs), and is used to prevent or treat patients with deep vein thrombosis (DVT) and pulmonary embolism. Enoxaparin is the most widely used LMWH for DVT prophylaxis following knee or hip replacement surgery. Common side effects of enoxaparin include bleeding, petechiae at the injection site, and thrombocytopenia. However, reactive thrombocytosis is a rarely reported adverse reaction. We managed a patient who developed enoxaparin-associated thrombocytosis, which was completely resolved after treatment cessation. Case presentation A 78-year-old female was hospitalized for post-hip replacement rehabilitation. Low molecular weight heparin 40 mg/day was administered subcutaneously to prevent deep venous thrombosis (DVT). At admission, her platelet count was normal (228 × 109/L) and her white blood cell count was slightly elevated (12.91 × 109/L). Seven days after admission, the patient developed thrombocytosis, which peaked on the 14th day (836 × 109/L), while her white blood cell count had returned to normal (8.86 × 109/L). Her therapeutic regimen was reviewed, and enoxaparin was identified as a potentially reversible cause of reactive thrombocytosis. Switching from enoxaparin to rivaroxaban lead to a gradual decrease in the patient’s platelet count, which eventually returned to normal levels 16 days after enoxaparin was discontinued. No complications secondary to thrombocytosis was observed, and no conclusion was reached on the use of small doses of aspirin for antithrombotic therapy under these circumstances. Conclusion Enoxaparin-induced reactive thrombocytosis should be suspected in patients with thrombocytosis following enoxaparin administration as an anticoagulant to prevent certain complications.

Diagnostic value of post-operative platelet-to-white blood cell ratio after splenectomy in patients with advanced ovarian cancer

2019 ◽  
Vol 29 (8) ◽  
pp. 1292-1297 ◽  
Author(s):  
Konstantinos Lathouras ◽  
Georgios Panagakis ◽  
Sarah Joanne Bowden ◽  
Konstantinos Saliaris ◽  
Srdjan Saso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Platelet Count ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Predictive Value ◽  
Blood Cell Count ◽  
Cell Ratio ◽  
Grade Iii

IntroductionSplenectomy-induced thrombocytosis and leukocytosis may obscure the early diagnosis of post-operative infection or sepsis. In trauma patients after splenectomy, a platelet-to-white blood cell ratio of <20 has been shown to reliably differentiate post-operative sepsis from transient physiological responses.ObjectiveTo determine whether the platelet-to-white blood cell ratio can be applied to differentiate between reactive post-operative changes and latent infection.MethodsAll consecutive patients with ovarian cancer who underwent splenectomy between January 2013 and October 2018 in two large European gynecological cancer centers were retrospectively evaluated. Main outcome measures were white blood cell count, platelet count, and platelet-to-white blood cell ratio on post-operative days 1, 5, and 7. These were correlated with surgical outcome and morbidity according to the Clavien-Dindo classification. A binomial logistic regression was applied to assess the predictive value of day 5 platelet-to-white blood cell ratio, white blood cell count, and platelet count for predicting grade III post-operative sepsis.ResultsNinety-five patients with ovarian cancer (mean age 54 years, range 18–75) were identified. Seventeen patients (17.9%) developed a grade III post-operative sepsis. In all post-operative patients, mean white blood cell count on day 5 decreased (from 15.4×103/μL to 11.4×103/μL), while the mean platelet count rose (from 260.7×103/μL to 385.3×103/μL). A high platelet count (>313×103/μL) failed to show any predictive value (OR=0.94; 95% CI 0.30 to 3.0; p=0.921). A low platelet-to-white blood cell ratio (<26) (OR=3.49; 95% CI 1.18 to 10.32; p=0.0241) and high white blood cell count (>14.5×103/μL) on day 5 (OR=11.0; 95% CI 3.3 to 36.2; p<0.001) were significant for predicting sepsis. Despite a significant OR, the sensitivity and specificity were low; day 5 platelet-to-white blood cell ratio at a cut-off point of 26 achieved a sensitivity of 72% and specificity of 53% (area under the curve 0.637, 95% CI 0.480 to 0.796) in predicting grade III post-operative sepsis.ConclusionsPlatelet-to-white blood cell ratio after cytoreductive surgery for ovarian cancer with splenectomy does not appear to have a strong predictive value in differentiating between sepsis and reactive splenectomy-induced changes. Leukocytosis, in combination with clinical assessment, may remain the most useful tool for prediction of sepsis after cytoreductive surgery with splenectomy.

scholarly journals Genetic overlap between idiopathic pulmonary fibrosis and COVID−19

2021 ◽  
Author(s):  
Richard J Allen ◽  
Beatriz Guillen-Guio ◽  
Emma Croot ◽  
Luke M Kraven ◽  
Samuel Moss ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Biological Processes ◽  
Genetic Loci ◽  
Genome Wide ◽  
Genetic Overlap ◽  
Causal Variants ◽  
Shared Genetic

AbstractGenome-wide association studies (GWAS) of coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) have identified genetic loci associated with both traits, suggesting possible shared biological mechanisms. Using updated GWAS of COVID-19 and IPF, we evaluated the genetic overlap between these two diseases and identified four genetic loci (including one novel) with likely shared causal variants between severe COVID-19 and IPF. Although there was a positive genetic correlation between COVID-19 and IPF, two of these four shared genetic loci had an opposite direction of effect. IPF-associated genetic variants related to telomere dysfunction and spindle assembly showed no association with COVID-19 phenotypes. Together, these results suggest there are both shared and distinct biological processes driving IPF and severe COVID-19 phenotypes.

scholarly journals Prioritization of genes associated with the pathogenesis of leukosis in cattle

2019 ◽  
Vol 22 (8) ◽  
pp. 1063-1069 ◽  
Author(s):  
N. S. Yudin ◽  
N. L. Podkolodnyy ◽  
T. A. Agarkova ◽  
E. V. Ignatieva
Keyword(s):  
Protein Interactions ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Mammalian Species ◽  
Genome Wide Association ◽  
Farm Animals ◽  
Genome Wide Association Studies ◽  
Protein Protein Interactions ◽  
Genome Wide ◽  
A Genome

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF,LTB,BOLA-DQA1,BOLA-DRB3,ATF2), which can affect the sensitivity/resistance of cattle to leukemia.

scholarly journals Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry

2018 ◽  
Vol 28 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Sara L Pulit ◽  
Charli Stoneman ◽  
Andrew P Morris ◽  
Andrew R Wood ◽  
Craig A Glastonbury ◽  
...  
Keyword(s):  
Body Fat ◽  
Association Studies ◽  
Meta Analysis ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.

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