Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease

Venous disease is a term that broadly covers both venous thromboembolic disease and chronic venous disease. The basic pathophysiology of venous thromboembolism and chronic venous disease differ as venous thromboembolism results from an imbalance of hemostasis and thrombosis while chronic venous disease occurs in the setting of tissue damage because of prolonged venous hypertension. Both diseases are common and account for significant mortality and morbidity, respectively, and collectively make up a large health care burden. Despite both diseases having well-characterized environmental components, it has been known for decades that family history is an important risk factor, implicating a genetic element to a patient’s risk. Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease. In this review, we will highlight the current state of knowledge on the epidemiology and genetics of venous thromboembolism and chronic venous disease and directions for future research.

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Four Loci Are Associated with Cardiorespiratory Fitness and Endurance Performance in Young Chinese Females

Scientific Reports ◽

10.1038/s41598-020-67045-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ying Zhao ◽

Guoyuan Huang ◽

Zuosong Chen ◽

Xiang Fan ◽

Tao Huang ◽

...

Keyword(s):

Cardiorespiratory Fitness ◽

Association Studies ◽

Endurance Performance ◽

Young Female ◽

Future Research ◽

Genome Wide Association Studies ◽

Genetic Trait ◽

Young Females ◽

Genome Wide ◽

Fixed Model

AbstractCardiorespiratory fitness (CRF) and endurance performance are characterized by a complex genetic trait with high heritability. Although research has identified many physiological and environmental correlates with CRF, the genetic architecture contributing to CRF remains unclear, especially in non-athlete population. A total of 762 Chinese young female participants were recruited and an endurance run test was used to determine CRF. We used a fixed model of genome-wide association studies (GWAS) for CRF. Genotyping was performed using the Affymetrix Axiom and illumina 1 M arrays. After quality control and imputation, a linear regression-based association analysis was conducted using a total of 5,149,327 variants. Four loci associated with CRF were identified to reach genome-wide significance (P < 5.0 × 10-8), which located in 15q21.3 (rs17240160, P = 1.73 × 10-9, GCOM1), 3q25.31 (rs819865, P = 8.56 × 10-9, GMPS), 21q22.3 (rs117828698, P = 9.59 × 10-9, COL18A1), and 17q24.2 (rs79806428, P = 3.85 × 10-8, PRKCA). These loci (GCOM1, GMPS, COL18A1 and PRKCA) associated with cardiorespiratory fitness and endurance performance in Chinese non-athlete young females. Our results suggest that these gene polymorphisms provide further genetic evidence for the polygenetic nature of cardiorespiratory endurance and be used as genetic biomarkers for future research.

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Pathophysiology and genetic factors in moyamoya disease

Neurosurgical FOCUS ◽

10.3171/2009.1.focus08302 ◽

2009 ◽

Vol 26 (4) ◽

pp. E4 ◽

Cited By ~ 74

Author(s):

Achal S. Achrol ◽

Raphael Guzman ◽

Marco Lee ◽

Gary K. Steinberg

Keyword(s):

Moyamoya Disease ◽

Genetic Factors ◽

Association Studies ◽

Vascular Anomalies ◽

Future Research ◽

Incomplete Penetrance ◽

Genome Wide Association Studies ◽

Research Directions ◽

Genome Wide ◽

Future Research Directions

Moyamoya disease is an uncommon cerebrovascular condition characterized by progressive stenosis of the bilateral internal carotid arteries with compensatory formation of an abnormal network of perforating blood vessels providing collateral circulation. The etiology and pathogenesis of moyamoya disease remain unclear. Evidence from histological studies, proteomics, and endothelial progenitor cell analyses suggests new theories underlying the cause of vascular anomalies, including moyamoya disease. Familial moyamoya disease has been noted in as many as 15% of patients, indicating an autosomal dominant inheritance pattern with incomplete penetrance. Genetic analyses in familial moyamoya disease and genome-wide association studies represent promising strategies for elucidating the pathophysiology of this condition. In this review, the authors discuss recent studies that have investigated possible mechanisms underlying the etiology of moyamoya disease, including stem cell involvement and genetic factors. They also discuss future research directions that promise not only to offer new insights into the origin of moyamoya disease but to enhance our understanding of new vessel formation in the CNS as it relates to stroke, vascular anomalies, and tumor growth.

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Polymorphisms Affecting Trace Element Bioavailability

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000039 ◽

2010 ◽

Vol 80 (45) ◽

pp. 314-318 ◽

Cited By ~ 3

Author(s):

John C. Mathers ◽

Catherine Méplan ◽

John E. Hesketh

Keyword(s):

Trace Element ◽

Individual Variation ◽

Association Studies ◽

Copy Number Variants ◽

Micro Rna ◽

Future Research ◽

Genome Wide Association Studies ◽

Complex Interactions ◽

Genome Wide ◽

Genes Encoding

This review outlines the nature of inter-individual variation in trace element bioavailability, focusing on genetic and epigenetic determinants. We note that pathogenic mutations responsible for dangerously high (or low) status for the micronutrient are unlikely to make large contributions to variability in bioavailability among the general population. Prospective genotyping (for variants in genes encoding selenoproteins) of participants in human studies illustrate one approach to understanding the complex interactions between genotype and trace element supply, which determine the functional bioavailability of selenium. Rapid advances in technological and bioinformatics tools; e. g., as used in Genome-Wide Association Studies, are opening new avenues for research on the genetic determinants of inter-individual variation in trace element bioavailability. This may include copy number variants in addition to the more widely studied polymorphisms. Future research on trace element bioavailability should encompass studies of epigenetic variants, including the role of non-coding (micro) RNA.

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Venous thromboembolism and prostate cancer: what about genetic markers?

Pharmacogenomics ◽

10.2217/pgs-2020-0094 ◽

2021 ◽

Vol 22 (6) ◽

pp. 365-373

Author(s):

Sofia Coelho Abreu ◽

Valéria Tavares ◽

Filipa Carneiro ◽

Rui Medeiros

Keyword(s):

Prostate Cancer ◽

Venous Thromboembolism ◽

Genetic Markers ◽

Association Studies ◽

Genome Wide Association ◽

Clinical Implications ◽

Genome Wide Association Studies ◽

Genetic Determinants ◽

Genome Wide ◽

The Relationship

Aim & methods: To review the existing literature concerning the relationship between venous thromboembolism (VTE) and prostate cancer (PC) and explore the putative biological and clinical implications of VTE genetic markers on PC patients by screening the PubMed database. Results: Considering the roles of VTE genome-wide association studies-identified genetic determinants in disease development in the general population, these variants might also underlie the susceptibility for PC-related VTE. Therefore, they could help to identify those with a positive benefit-to-harm ratio for thromboprophylaxis approaches during cancer therapy management, thereby improving patient’s prognosis. Conclusion: Future studies are mandatory to explore the relationship between VTE and PC and dissect the predictive value of VTE genome-wide association studies-identified genetic determinants in PC patients, given their clinical implications.

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What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review

Psychological Medicine ◽

10.1017/s0033291715000537 ◽

2015 ◽

Vol 45 (12) ◽

pp. 2461-2480 ◽

Cited By ~ 55

Author(s):

R. Gurung ◽

D. P. Prata

Keyword(s):

Bipolar Disorder ◽

Brain Structure ◽

Association Studies ◽

Structure And Function ◽

Future Research ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Brain Structure And Function ◽

And Function ◽

The Impact

The powerful genome-wide association studies (GWAS) revealed common mutations that increase susceptibility for schizophrenia (SZ) and bipolar disorder (BD), but the vast majority were not known to be functional or associated with these illnesses. To help fill this gap, their impact on human brain structure and function has been examined. We systematically discuss this output to facilitate its timely integration in the psychosis research field; and encourage reflection for future research. Irrespective of imaging modality, studies addressing the effect of SZ/BD GWAS risk genes (ANK3, CACNA1C, MHC, TCF4, NRGN, DGKH, PBRM1, NCANandZNF804A) were included. Most GWAS risk variations were reported to affect neuroimaging phenotypes implicated in SZ/BD: white-matter integrity (ANK3andZNF804A), volume (CACNA1CandZNF804A) and density (ZNF804A); grey-matter (CACNA1C, NRGN, TCF4andZNF804A) and ventricular (TCF4) volume; cortical folding (NCAN) and thickness (ZNF804A); regional activation during executive tasks (ANK3, CACNA1C, DGKH, NRGNandZNF804A) and functional connectivity during executive tasks (CACNA1CandZNF804A), facial affect recognition (CACNA1CandZNF804A) and theory-of-mind (ZNF804A); but inconsistencies and non-replications also exist. Further efforts such as standardizing reporting and exploring complementary designs, are warranted to test the reproducibility of these early findings.

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Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management?

International Journal of Molecular Sciences ◽

10.3390/ijms22084182 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4182

Author(s):

Michal Vrablik ◽

Dana Dlouha ◽

Veronika Todorovova ◽

Denes Stefler ◽

Jaroslav A. Hubacek

Keyword(s):

Cardiovascular Disease ◽

Risk Prediction ◽

Association Studies ◽

Risk Scores ◽

Genome Wide Association Studies ◽

Cvd Risk ◽

Mortality And Morbidity ◽

New Genes ◽

Gene Environment ◽

Genome Wide

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. Although the use of genetic risk scores further improves CVD prediction, the significance is not unambiguous, and some subjects at risk remain undetected. Further research directions should focus on the “second level” of genetic information, namely, regulatory molecules (miRNAs) and epigenetic changes, predominantly DNA methylation and gene-environment interactions.

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Genetic contributions to anxiety disorders: where we are and where we are heading

Psychological Medicine ◽

10.1017/s0033291720005486 ◽

2021 ◽

pp. 1-16

Author(s):

Helga Ask ◽

Rosa Cheesman ◽

Eshim S. Jami ◽

Daniel F. Levey ◽

Kirstin L. Purves ◽

...

Keyword(s):

Anxiety Disorders ◽

Psychiatric Disorders ◽

Large Scale ◽

Current Knowledge ◽

Association Studies ◽

Twin Studies ◽

Future Research ◽

Specific Gene ◽

Genome Wide Association Studies ◽

Genome Wide

Abstract Anxiety disorders are among the most common psychiatric disorders worldwide. They often onset early in life, with symptoms and consequences that can persist for decades. This makes anxiety disorders some of the most debilitating and costly disorders of our time. Although much is known about the synaptic and circuit mechanisms of fear and anxiety, research on the underlying genetics has lagged behind that of other psychiatric disorders. However, alongside the formation of the Psychiatric Genomic Consortium Anxiety workgroup, progress is rapidly advancing, offering opportunities for future research. Here we review current knowledge about the genetics of anxiety across the lifespan from genetically informative designs (i.e. twin studies and molecular genetics). We include studies of specific anxiety disorders (e.g. panic disorder, generalised anxiety disorder) as well as those using dimensional measures of trait anxiety. We particularly address findings from large-scale genome-wide association studies and show how such discoveries may provide opportunities for translation into improved or new therapeutics for affected individuals. Finally, we describe how discoveries in anxiety genetics open the door to numerous new research possibilities, such as the investigation of specific gene–environment interactions and the disentangling of causal associations with related traits and disorders. We discuss how the field of anxiety genetics is expected to move forward. In addition to the obvious need for larger sample sizes in genome-wide studies, we highlight the need for studies among young people, focusing on specific underlying dimensional traits or components of anxiety.

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Invited review: Genome-wide association analysis for quantitative traits in livestock – a selective review of statistical models and experimental designs

Archives Animal Breeding ◽

10.5194/aab-60-335-2017 ◽

2017 ◽

Vol 60 (3) ◽

pp. 335-346 ◽

Cited By ~ 17

Author(s):

Markus Schmid ◽

Jörn Bennewitz

Keyword(s):

Statistical Models ◽

Complex Traits ◽

Quantitative Traits ◽

Association Studies ◽

Real Data ◽

Genome Wide Association ◽

Future Research ◽

Genome Wide Association Studies ◽

Livestock Breeding ◽

Genome Wide

Abstract. Quantitative or complex traits are controlled by many genes and environmental factors. Most traits in livestock breeding are quantitative traits. Mapping genes and causative mutations generating the genetic variance of these traits is still a very active area of research in livestock genetics. Since genome-wide and dense SNP panels are available for most livestock species, genome-wide association studies (GWASs) have become the method of choice in mapping experiments. Different statistical models are used for GWASs. We will review the frequently used single-marker models and additionally describe Bayesian multi-marker models. The importance of nonadditive genetic and genotype-by-environment effects along with GWAS methods to detect them will be briefly discussed. Different mapping populations are used and will also be reviewed. Whenever possible, our own real-data examples are included to illustrate the reviewed methods and designs. Future research directions including post-GWAS strategies are outlined.

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Genome-wide association studies suggest limited immune gene enrichment in schizophrenia compared to five autoimmune diseases

10.1101/030411 ◽

2015 ◽

Cited By ~ 2

Author(s):

Jennie G. Pouget ◽

Vanessa F. Gonçalves ◽

Sarah L. Spain ◽

Hilary K. Finucane ◽

Soumya Raychaudhuri ◽

...

Keyword(s):

Association Studies ◽

Genome Wide Association ◽

Future Research ◽

Immune Gene ◽

Genome Wide Association Studies ◽

Immune Genes ◽

Genome Wide ◽

Immune Alterations ◽

Pathway Analyses ◽

Immune Loci

AbstractThere has been intense debate over the immunological basis of schizophrenia, and the potential utility of adjunct immunotherapies. The major histocompatibility complex is consistently the most powerful region of association in genome-wide association studies (GWASs) of schizophrenia, and has been interpreted as strong genetic evidence supporting the immune hypothesis. However, global pathway analyses provide inconsistent evidence of immune involvement in schizophrenia, and it remains unclear whether genetic data support an immune etiology per se. Here we empirically test the hypothesis that variation in immune genes contributes to schizophrenia. We show that there is no enrichment of immune loci outside of the MHC region in the largest genetic study of schizophrenia conducted to date, in contrast to five diseases of known immune origin. Among 108 regions of the genome previously associated with schizophrenia, we identify six immune candidates (DPP4, HSPD1, EGR1, CLU, ESAM, NFATC3) encoding proteins with alternative, nonimmune roles in the brain. While our findings do not refute evidence that has accumulated in support of the immune hypothesis, they suggest that genetically mediated alterations in immune function may not play a major role in schizophrenia susceptibility. Instead, there may be a role for pleiotropic effects of a small number of immune genes that also regulate brain development and plasticity. Whether immune alterations drive schizophrenia progression is an important question to be addressed by future research, especially in light of the growing interest in applying immunotherapies in schizophrenia.

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Single- and Multimarker Genome-Wide Scans Evidence Novel Genetic Risk Modifiers for Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0041-1723988 ◽

2021 ◽

Author(s):

Marisol Herrera-Rivero ◽

Monika Stoll ◽

Jana-Charlotte Hegenbarth ◽

Frank Rühle ◽

Verena Limperger ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cardiovascular Diseases ◽

Association Studies ◽

Strong Support ◽

Susceptibility Genes ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Susceptibility Factors ◽

Gene Level

AbstractPrevious genome-wide association studies (GWASs) have established several susceptibility genes for venous thromboembolism (VTE) and suggested many others. However, a large proportion of the genetic variance in VTE remains unexplained. Here, we report genome-wide single- and multimarker as well as gene-level associations with VTE in 964 cases and 899 healthy controls of European ancestry. We report 19 loci at the genome-wide level of association (p ≤ 5 × 10−8). Our results add to the strong support for the association of genetic variants in F5, NME7, ABO, and FGA with VTE, and identify several loci that have not been previously associated with VTE. Altogether, our novel findings suggest that 20 susceptibility genes for VTE were newly discovered by our study. These genes may impact the production and prothrombotic functions of platelets, endothelial cells, and white and red blood cells. Moreover, the majority of these genes have been previously associated with cardiovascular diseases and/or risk factors for VTE. Future studies are warranted to validate our findings and to investigate the shared genetic architecture with susceptibility factors for other cardiovascular diseases impacting VTE risk.

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