scholarly journals The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Walsh ◽  
F Mazzarotto ◽  
M Hawley ◽  
M Beltrami ◽  
L Beekman ◽  
...  
Keyword(s):  
Association Analysis ◽  
Rare Variant ◽  
Genetic Architecture ◽  
Left Ventricular ◽  
Myocardial Wall ◽  
Genetic Landscape ◽  
The Subject ◽  
The Relationship ◽  
Population Controls ◽  
Secondary Phenotype

Abstract Background Left ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. Purpose To investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies. Methods We performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases. Results We observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes. Conclusions We demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted. Cardiomyopathy rare variant frequencies Funding Acknowledgement Type of funding source: None

scholarly journals The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases

2020 ◽  
Author(s):  
Francesco Mazzarotto ◽  
Megan H. Hawley ◽  
Matteo Beltrami ◽  
Leander Beekman ◽  
Antonio de Marvao ◽  
...  
Keyword(s):  
Association Analysis ◽  
Genetic Architecture ◽  
Left Ventricular ◽  
Myocardial Wall ◽  
Genetic Landscape ◽  
The Subject ◽  
The Uk ◽  
The Relationship ◽  
Population Controls ◽  
Secondary Phenotype

AbstractBackgroundLeft ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. We sought to investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies.MethodsWe performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases.ResultsWe observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants in MYH7, ACTN2 and PRDM16 may represent a distinct LVNC aetiology. MYH7 truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Individuals with MYH7 truncating variants identified in the UK Biobank and cohorts of healthy volunteers also displayed significantly greater non-compaction compared to matched controls, with 50% meeting the diagnostic criteria for LVNC. Additionally, structural variants (exon deletions) in RYR2 and missense variants in the transmembrane region of HCN4 were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes.ConclusionsWe demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted.

scholarly journals Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies

2021 ◽  
Author(s):  
Francesco Mazzarotto ◽  
Megan H. Hawley ◽  
Matteo Beltrami ◽  
Leander Beekman ◽  
Antonio de Marvao ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Large Scale ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Large Scale Assessment ◽  
Genetic Overlap ◽  
The Uk ◽  
Population Controls ◽  
Secondary Phenotype

Abstract Purpose To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. Methods We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. Conclusion LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.

scholarly journals Exautomate: A user-friendly tool for region-based rare variant association analysis (RVAA)

2019 ◽  
Author(s):  
Brent D. Davis ◽  
Jacqueline S. Dron ◽  
John F. Robinson ◽  
Robert A. Hegele ◽  
Dan J. Lizotte
Keyword(s):  
Association Analysis ◽  
Rare Variant ◽  
Complex Traits ◽  
Genetic Architecture ◽  
Rare Variants ◽  
Great Promise ◽  
Rare Variant Association ◽  
Complex Phenotypes ◽  
Rare Genetic Variation ◽  
User Friendly

AbstractRegion-based rare variant association analysis (RVAA) is a popular method to study rare genetic variation in large datasets, especially in the context of complex traits and diseases. Although this method shows great promise in increasing our understanding of the genetic architecture of complex phenotypes, performing a region-based RVAA can be challenging. The sequence kernel association test (SKAT) can be used to perform this analysis, but its inputs and modifiable parameters can be extremely overwhelming and may lead to results that are difficult to reproduce. We have developed a software package called “Exautomate” that contains the tools necessary to run a region-based RVAA using SKAT and is easy-to-use for any researcher, regardless of their previous bioinformatic experiences. In this report, we discuss the utilities of Exautomate and provide detailed examples of implementing our package. Importantly, we demonstrate a proof-of-principle analysis using a previously studied cohort of 313 familial hypercholesterolemia (FH) patients. Our results show an increased burden of rare variants in genes known to cause FH, thereby demonstrating a successful region-based RVAA using Exautomate. With our easy-to-use package, we hope researchers will be able to perform reproducible region-based RVAA to further our collective understanding behind the genetics of complex traits and diseases.

The relationship of the scleractinian corals to the rugose corals

Paleobiology ◽  
1980 ◽  
Vol 6 (02) ◽  
pp. 146-160 ◽  
Author(s):  
William A. Oliver
Keyword(s):  
Critical Points ◽  
Scleractinian Corals ◽  
Convincing Evidence ◽  
Early Triassic ◽  
Rugose Corals ◽  
History Of ◽  
The Subject ◽  
Relationship Of ◽  
The Relationship ◽  
Biologic Factors

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.

HUBUNGAN GAYA BELAJAR SISWA TERHADAP ASPEK PENGETAHUAN SISWA PADA MATA PELAJARAN SISTEM KOMPUTER DI SMK IT RAHMATAN KARIMAH BENGKULU TENGAH

2020 ◽  
Vol 1 (01) ◽  
pp. 13-20
Author(s):  
Dian Saputra
Keyword(s):  
Learning Styles ◽  
Computer System ◽  
Learning Style ◽  
Descriptive Analysis ◽  
Visual Learning ◽  
Auditory Learning ◽  
Analysis Techniques ◽  
Post Test ◽  
The Subject ◽  
The Relationship

This study aims to find out the relationship between learning style and students’ knowledge aspect on Computer System Subject at SMK IT Rahmatan Karimah of  Central Bengkulu, the type of research is quantitative and the subject of research is grade X in SMK IT Rahmatan Karimah of  Central Bengkulu. Data collection techniques using observation, Questionnaire and documentation. Data analysis techniques used were Descriptive Analysis, and inferential Statistical Analysis. The results of visual learning style post-test were 11 people with a mean of 76.36, an auditory learning style of 8 people at a mean of 62.14, a kinesthetic learning style of 3 people at a mean of 50.33, apart from that (r x y = 2.35) and the magnitude of r is reflected in the table (r table = 0.4132). Then rxy > r table ie = 2.35> 0.4132. In other words, Ho is rejected and Ha is accepted. It has a significant relationship between the learning styles of students and students’ knowledge aspect on Computer System Subject of grade X TKJ in SMK IT Rahmatan Karimah of  Central Bengkulu

The Miracles and Cult of St Margaret of Scotland

2018 ◽  
Vol 97 (1) ◽  
pp. 1-11 ◽  
Author(s):  
SangDong Lee
Keyword(s):  
Historical Research ◽  
The Subject ◽  
The Relationship

Queen Margaret (1070–93) has been the subject of much historical research. Previous studies of the queen and later saint have been undertaken from several different perspectives, including the biographical, institutional and hagiographical. In addition, some scholars have focused on her piety and later cult. Although a saint's miracles were one of the significant elements affecting the development of a cult, far less interest has been shown in the geopolitical importance of the miracles attributed to St Margaret and the relationship between the miracles and the saint's cult. The intention of this paper is to examine the miracles attributed to St Margaret and to identify their characteristics within the context of their contribution to, and influence in, the development of her cult.

The Priority of Democracy

2011 ◽  
Author(s):  
Jack Knight ◽  
James Johnson
Keyword(s):  
Decision Making ◽  
Monetary Policy ◽  
Political Institutions ◽  
Federal Reserve ◽  
Democratic Politics ◽  
Institutional Choice ◽  
Democratic Process ◽  
Strong Case ◽  
The Subject ◽  
The Relationship

Pragmatism and its consequences are central issues in American politics today, yet scholars rarely examine in detail the relationship between pragmatism and politics. This book systematically explores the subject and makes a strong case for adopting a pragmatist approach to democratic politics—and for giving priority to democracy in the process of selecting and reforming political institutions. What is the primary value of democracy? When should we make decisions democratically and when should we rely on markets? And when should we accept the decisions of unelected officials, such as judges or bureaucrats? This book explores how a commitment to pragmatism should affect our answers to such important questions. It concludes that democracy is a good way of determining how these kinds of decisions should be made—even if what the democratic process determines is that not all decisions should be made democratically. So, for example, the democratically elected U.S. Congress may legitimately remove monetary policy from democratic decision-making by putting it under the control of the Federal Reserve. This book argues that pragmatism offers an original and compelling justification of democracy in terms of the unique contributions democratic institutions can make to processes of institutional choice. This focus highlights the important role that democracy plays, not in achieving consensus or commonality, but rather in addressing conflicts. Indeed, the book suggest that democratic politics is perhaps best seen less as a way of reaching consensus or agreement than as a way of structuring the terms of persistent disagreement.

Zur Pragmatik und Grammatik der Wissenschaftskommunikation. Ein Modellierungsvorschlag

Fachsprache ◽  
2017 ◽  
Vol 33 (1-2) ◽  
pp. 36-60
Author(s):  
Mathilde Hennig ◽  
Dániel Czicza
Keyword(s):  
Language Variation ◽  
Common Language ◽  
Passive Voice ◽  
The Subject ◽  
The Relationship ◽  
Communication In Science

The article aims to examine grammatical features and pragmatic concerns of communicating in the sciences. In the research of certain languages, it became common to explaingrammatical features such as the usage of passive voice and nominal structures by communication requirements such as objectivity and precision. With the assumption that communication in science is designed to help gain and spread new insight, the authors tried to integrate several approaches to pragmatic and grammatical features of communication. By discussing the relationship between the grammar of certain languages and of the corresponding common language, the article also places the subject of communication in the sciences in the discipline of language variation.

Learning Language Levels in Students Accurate with a History Academic Achievement History

2017 ◽  
Vol 1 (2) ◽  
pp. 137
Author(s):  
Noorlela Binti Noordin ◽  
Abdul Razaq Ahmad ◽  
Anuar Ahmad
Keyword(s):  
Academic Achievement ◽  
Statistical Inference ◽  
Quantitative Data ◽  
Quantitative Methods ◽  
Descriptive Statistics ◽  
Language Test ◽  
The Subject ◽  
The Difference ◽  
Learning Language ◽  
The Relationship

This study was aimed to evaluate the Malay proficiency among students in Form Two especially non-Malay students and its relationship to academic achievement History. To achieve the purpose of the study there are two objectives, the first is to look at the difference between mean of Malay Language test influences min of academic achievement of History subject among non-Malay students in Form Two and the second is the relationship between the level of Malay proficiency and their academic achievement for History. This study used quantitative methods, which involved 100 people of Form Two non-Malay students in one of the schools in Klang, Selangor. This study used quantitative data were analyzed using descriptive statistics and statistical inference with IBM SPSS Statistics v22 software. This study found that there was a relationship between the proficiency of Malay language among non-Malay students with achievements in the subject of History. The implications of this study are discussed in this article.

Educación y valores

2014 ◽  
pp. 83
Author(s):  
Sabino de Juan López
Keyword(s):  
Key Words ◽  
A Priori ◽  
Palabras Clave ◽  
The Subject ◽  
The Relationship ◽  
Problem Of The Criterion

RESUMEN En el artículo se ofrece una reflexión en torno a la educación y valores. Tras una referencia a los diferentes sentidos en que se puede plantear el problema en función de la forma como se puede entender la relación entre los dos sustantivos “educación” y “valores”, la reflexión se centra en algunos problemas relacionados con los valores en cuanto contenidos de la educación. Primeramente se refiere al problema del criterio en función del cual determinar los valores de la educación, concluyendo en que el criterio no podía ser ni de carácter a priori, ni empírico, sino “sintético”. A continuación, se afronta el problema del principio, de la fuente de los valores, o la concreción del criterio de los valores de la educación, entendiendo que éstos deberían ser determinados a partir del sujeto de la educación. Se concluye con la referencia a una exigencia de los valores de la educación, la configuración de una totalidad unitaria e interactiva. Palabras clave: educación, valores, fuente de valores, integración, cultura EDUCATION AND VALUES ABSTRACT The article offers a reflection on education and values. After a reference to the different senses in which one can pose the problem in terms of how you can understand the relationship between the two nouns “education” and “values”, reflection focuses on some problems related to the values in the contents of education. First, it concerns the problem of the criterion against which to determine the values of education, concluding that the criterion could be neither a priori in nature, not empirical, but “synthetic”. Herein, the problem of principle is faced, the source of values, or the realization of the criterion of the values of education, understanding that these should be determined from the subject of education. It concludes with the reference of a requirement of the values in education, setting up a unitary and interactive whole. Key Words: education, values , power values , integration, culture

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