Getting Personal: Omics of the Heart

About Getting Personal: Omics of the Heart

Each monthly episode will discuss recent publications in the fields of genomics and precision medicine of cardiovascular disease.

Publisher

Jane Ferguson

Category

health & fitness · science

Language

en

Explicit

No

First episode

21 Sept 2017

Latest episode

8 Apr 2020

Latest episodes

37 episodes in the feed.

1. 

   8 Apr 2020

   February 2020

   Jane Ferguson:                  Hi there. Welcome to Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson, and this is Episode 36 from February 2020. First up, we have “Identification of Circulating Proteins Associated with Blood Pressure Using Mendelian Randomization” from Sébastien Thériault, Guillaume Paré, and colleagues from McMaster University in Ontario. They set out to assess whether they could identify protein biomarkers of hypertension using a Mendelian randomization approach. They analyzed data from a genome-wide association study of 227 biomarkers which were profiled on a custom Luminex-based platform in over 4,000 diabetic or prediabetic participants of the origin trial. They constructed genetic predictors of each protein and then used these as instruments for Mendelian randomization. They obtained systolic and diastolic blood pressure measurements in almost 70,000 individuals, in addition to mean arterial pressure and pulse pressure in over 74,000 individuals, all European ancestry with GWAS data, as part of the International Consortium for Blood Pressure. Out of the 227 biomarkers tested, six of them were significantly associated with blood pressure traits by Mendelian randomization after correction for multiple testing. These included known biomarkers such as NT-proBNP, but also novel associations including urokinase-type plasminogen activator, adrenomedullin, interleukin-16, cellular fibronectin and insulin-like growth factor binding protein-3. They validated all of the associations apart from IL-16 in over 300,000 participants in UK Biobank. They probed associations with other cardiovascular risk markers and found that NT-proBNP associated with large artery atherosclerotic stroke, IGFBP3 associated with diabetes, and CFN associated with body mass index. This study identified novel biomarkers of blood pressure, which may be causal in hypertension. Further study of the underlying mechanisms is required to understand whether these could be useful therapeutic targets in hypertensive disease. The next paper comes from Sony Tuteja, Dan Rader, Jay Giri and colleagues from the University of Pennsylvania and it's entitled, “Prospective CYP2C19 Genotyping to Guide Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Pragmatic Randomized Clinical Trial”. They designed a pharmacode genomic trial to assess effects of CYP2C19 genotyping on antiplatelet therapy following PCI. Because loss of function alleles in CYP2C19 impair the effectiveness of clopidogrel, the team were interested in understanding whether knowledge of genotype status would affect prescribing in a clinical setting. They randomized 504 participants to genotype guided or usual care groups and assessed the rate of prasugrel or ticagrelor prescribing in place of clopidogrel within each arm. As a secondary outcome, they assessed whether prescribers adhere to genotype guided recommendations. Of genotyped individuals, 28% carried loss of function alleles. Within the genotype guided group overall, there was higher use of prasugrel or ticagrelor with these being prescribed to 30% of patients compared with only 21% in the usual care group. Within genotype individuals carrying loss of function alleles, 53% were started on prasugrel or ticagrelor, demonstrating some adherence to genotype guided recommendations. However, this also meant that 47% of people whose genotype suggested reduced effectiveness were nevertheless prescribed clopidogrel. This study highlights that even when genotype information is available, interventional cardiologists consider clinical factors such as disease presentation and may weight these more highly than genotype information when selecting antiplatelet therapy following PCI. The next paper is about “Deep Mutational Scan of an SCN5A Voltage Sensor and comes to us from Andrew Glazer, Dan Roden and colleagues from Vanderbilt University Medical Center. In this paper, the team aim to characterize the functional consequences of variants and the S4 voltage sensor of domain IV and the SCN5A gene using a high throughput method that they developed. SCN5A encodes the major voltage gated sodium channel in the heart and variants in SCN5A can cause multiple distinct genetic arrhythmia syndromes, including Brugada syndrome, long QT syndrome, atrial fibrillation, and dilated cardiomyopathy, and have been linked to sudden cardiac death. Because of this, there's considerable interest in understanding the functional and clinical consequences of different variants, but previous approaches were time consuming and results were often inconclusive with many variants being classified as uncertain significance. This newly developed deep mutational scanning approach allows for simultaneous assessment of the function of thousands of variants, making it much more efficient than low throughput patch clamping. The team assessed the function of 248 variants using a triple drug assay in HEK293T cells expressing each variant and they identified 40 putative gain of function and 33 putative loss of function variants. They successfully validated eight of nine of these by patch clamping data. Their study highlights the effectiveness of this deep mutational scanning approach for investigating variants in the cardiac sodium channel SCN5A gene and suggests that this may also be an effective approach for investigating putative disease variants and other ion channels. The next article is a research letter from Connor Emdin, Amit Khera, and colleagues from Mass General Hospital in the Broad Institute entitled, “Genome-Wide Polygenic Score and Cardiovascular Outcomes with Evacetrapib in Patients with High-Risk Vascular Disease: A Nested Case-Control Study”. In this study, the team set out to probe the utility of using polygenic risk scores to predict the risk of major adverse cardiovascular events within individuals already known to be at high cardiovascular risk and to assess whether genetic scores can identify individuals who would benefit from the use of a CETP inhibitor such as Evacetrapib. They analyze data from the ACCELERATE trial which had tested Evacetrapib in a high risk population, and they found no effect on the incidents of major adverse cardiovascular events overall. Within a nested case-control sample of individuals experiencing major CVD events versus no events, they applied a polygenic risk score and found that the score predicted major cardiovascular events. Patients in the highest quintile of the risk score were at 60% higher risk of a major cardiovascular event than patients in the lowest quintile. There was no evidence of any interaction between the genetic risk score and Evacetrapib. These data suggest that genetic risk scores may have utility in identifying individuals at high risk events but may not have utility in identifying individuals who may derive more benefit from CETP inhibition. The next letter concerns “Epigenome-Wide Association Study Identifies a Novel DNA Methylation in Patients with Severe Aortic Valve Stenosis” and comes from Takahito Nasu, Mamoru Satoh, Makoto Sasaki and colleagues from Iwate Medical University in Japan. They were interested in understanding whether differences in DNA methylation could underlie the risk of aortic valve stenosis. They conducted an EWAS or epigenome-wide association study of peripheral blood mononuclear cells or PBMCs from 44 individuals with aortic stenosis and 44 disease free controls. They collected samples at baseline before a surgical intervention in the individuals with aortic stenosis and collected a follow-up sample one year later. They found that DNA methylation at a site on chromosome eight mapping to the TRIB1, or tribbles homolog one gene, was lower in the aortic stenosis group than in the controls at baseline. They replicated the association in an independent sample of 50 cases and 50 controls. TRIB1 MRNA levels were higher in the aortic stenosis group than the controls. When they looked at methylation status one year after aortic valve replacement or a transcatheter aortic valve implantation in patients with stenosis, they found that DNA methylation had increased in the cases while TRIB1 MRNA decreased. These data suggests that methylation status of TRIB1 and expression of TRIB1 may relate to the disease processes in aortic stenosis such as hemodynamic dysregulation and they can be reversed through surgical intervention. Changes in the methylation status of TRIB1 could be a novel biomarker of response to aortic valve replacement. The next letter comes from Niels Grote Beverborg, Pim van der Harst, and colleagues from University Medical Center Groningen and is entitled, “Genetically Determined High Levels of Iron Parameters Are Protective for Coronary Artery Disease”. Their study addresses the conflicting hypotheses that high iron status is either deleterious or protective against cardiovascular disease. The team constructed genetic predictors of serum iron status using 11 previously identified snips and tested the genetic association with CAD in UK Biobank data from over 408,000 white participants. Overall, the genetic score for higher iron status was associated with protection against CAD. Ten of the snips suggested individual neutral or protective effects of higher iron status on CAD, while one iron increasing snip was associated with increased risk of disease but this was thought to be likely through an iron independent mechanism. Overall, these data suggest that a genetic predisposition to higher iron status does not increase risk of CAD and is actually protective against disease. The final letter is entitled, “Confidence Weighting for Robust Automated Measurements of Popliteal Vessel Wall MRI” and comes from Daniel Hippe, Jenq-Neng Hwang, and colleagues from the University of Washington. They were interested in assessing whether images of popliteal artery wall incidentally obtained during knee MRI as part of an osteoarthritis study could be used to study the development and progression of atherosclerosis. They developed an automated deep learning based algorithm to segment and quantify the popliteal artery wall in images obtained over 10 years in over 4,700 individuals. Their approach, which they named FRAPPE, or fully automated and robust analysis technique for popliteal artery evaluation, was able to reduce the average time required for segmentation analysis from four hours to eight minutes per image. They applied weights based on confidence for each segment to automatically improve the accuracy of aggregate measurements such as mean wall thickness or mean lumen area. Their data suggest that this automated method can rapidly generate useful information on atherosclerosis from MRI images obtained as part of other studies. When combined with other data. This approach may facilitate novel discovery in secondary analyses of existing studies in an efficient and cost effective way. And that's all for issue one of 2020. Come back next time for more of the latest papers from Circulation: Genomic and Precision Medicine. Speaker 2:                           This podcast is copyright American Heart Association 2020.

2. 

   8 Apr 2020

   December 2019

   Jane Ferguson:                  Hi, everyone. Welcome to episode 35 of Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson, an assistant professor of medicine at Vanderbilt University Medical Center, and an associate editor at Circulation: Genomic and Precision Medicine. This episode is first airing in December 2019. Let's see what we published this month. Our first paper is an “Integrated Multiomics Approach to Identify Genetic Underpinnings of Heart Failure and Its Echocardiographic Precursors: The Framingham Heart Study” from Charlotte Anderson, Ramachandran Vasan and colleagues from Herlev and Gentofte Hospital, Denmark and Boston University. In this paper, the team investigated the genomics of heart failure, combining GWAS with methylation and gene expression data, to prioritize candidate genes. They analyzed four heart failure related and eight echocardiography related phenotypes in several thousand individuals, and then identified SNPs, methylation markers, and differential gene expression associated with those phenotypes. They then created scores for each gene, based on the rank of statistical significance, aggregated across the different omics analysis. They examined the top ranked genes for evidence of pathway enrichment, and also looked up top SNPs for PheWAS associations in UK Biobank, and examined tissue specific expression in public data. While their data cannot definitively identify causal genes, they highlight several genes of potential relevance to heart failure pathogenesis, which may be promising candidates for future mechanistic studies. The next paper is “Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation” and comes from Elias Allara, Stephen Burgess and colleagues, from the University of Cambridge and the INVENT consortium. While it has been established, therapies to lower LDL cholesterol and triglycerides lead to lower risk of coronary artery disease, it remains less clear whether these lipid lowering efforts can also reduce risk for other cardiovascular outcomes. The team set out to address this question using Mendelian randomization. They generated genetic predictors of LDL cholesterol and triglycerides using data from the Global Lipids Genetics Consortium, and then assessed whether genetically predicted increased LDL and triglycerides associated with risk of cardiovascular phenotypes using UK Biobank data. Beyond CAD, they found that higher LDL was associated with abdominal aortic aneurysm and aortic valve stenosis. High triglyceride levels were positively associated with aortic valve stenosis and hypertension, but inversely associated with venous thromboembolism and hemorrhagic stroke. High LDL cholesterol and triglycerides were also associated with heart failure, which appeared to be mediated by CAD. Their data suggests that LDL lowering may have additional cardiovascular benefits in reducing aortic aneurism and aortic stenosis, while efforts to lower triglycerides may reduce the risk of aortic valve stenosis, but could result in increased thromboembolic risk. Next up is a paper from Steven Joffe, G.L. Splansky and colleagues, from the University of Pennsylvania and Boston University, on “Preferences for Return of Genetic Results Among Participants in the Jackson Heart Study and Framingham Heart Study”. There has been increasing discussion and concern about how to handle genetic data, and whether genetic results should be returned to participants, and under which circumstances. In this study, the teams that had to assess what participants themselves think. They query participants in the Jackson Heart Study, the Framingham Heart Study and the FHS Omni cohort, presenting them with potential scenarios that varied by five factors including phenotype severity, actionability, reproductive significance and relative of the absolute risk of the phenotype. Across all scenarios, 88 to 92% of respondents said that they would definitely or probably want to learn their result. In Jackson Heart Study respondents, factors increasing the desire for results included a positive attitude towards genetic testing, lower education, higher subjective numeracy, and younger age. The five pre-identified factors did not affect desire to receive results in Jackson Heart Study. Among Framingham Heart Study respondents, desire for results was associated with higher absolute risk, presentability, reproductive risk and positive attitudes towards genetic testing. Among FHS Omni respondents, desire for results was associated with positive attitudes towards genetic testing and younger age. Overall, these data show that across a variety of studies, there a high level of interest in receiving genetic results and that these are not necessarily linked to the phenotype or clinical significance of the results themselves. The next paper concerns “Peripheral Blood RNA Levels of QSOX1 and PLBD1 Are New Independent Predictors of Left Ventricular Dysfunction after Acute Myocardial Infarction” and this comes from Martin Vanhaverbeke, Peter Sinnaeve and colleagues, from University Hospital Leuven. They were interested in understanding whether they could identify subsequent left ventricular dysfunction in patients who suffered an acute myocardial infarction. They obtained blood and performed RNA-Seq at multiple time points in 143 individuals, following acute MI, to identify transcripts that were associated with subsequent LV dysfunction. They validated candidate gene transcripts in a validation sample of 449 individuals, confirming that expression of QSOX1 and PLBD1 at admission, were associated with LV dysfunction at follow-up. Adding QSOX1 to a model, consisting of clinical variables and cardiac biomarkers, including NT proBNP, had an incremental predictive value. They took their findings to a pig model and found that whole blood expression of both genes was associated with neutrophil infiltration in these ischemic myocardium. This study suggests that expression of QSOX1 and PLBD1 following MI, may have utility in predicting development of LV dysfunction and may be markers of cardiac inflammation. The next paper is a research letter from Hanna Hanania, Denver Sallee and Dianna Milewicz, from the University of Texas Health Science Center, and Emory University School of Medicine. Who set out to answer the question, “Do HCN4 Variants Predisposed to Thoracic Aortic Aneurysms and Dissections?” Previous work has suggested that rare variants in HCN4 associated with thoracic aortic disease, including ascending aortic dilation, left ventricular noncompaction cardiomyopathy, and sinus bradycardia. However, the evidence for disease segregation was relatively weak. The team set out to explore these potential associations using exome sequencing data from 521 individuals, from 347 unrelated families with heritable thoracic aortic disease, as well as 355 individuals with early onset sporadic aortic dissections, but no family history of disease. They identified a missense variant G482R, which segregated with disease in four unrelated families, was absent from the nomad database and was predicted to disrupt protein function and have deleterious effects. Their data support the evidence that HCN4 rare variants can cause heritable thoracic aortic disease with left ventricular noncompaction cardiomyopathy and bradycardia. Our final paper is a white paper from H. Li, X. J. Luo and colleagues, from the National Heart, Lung and Blood Institute at the NIH, and will likely interest anybody who applies for NIH grants, which I'm assuming is most of you listening to this podcast. Their paper on, “Portfolio Analysis of Research Grants in Data Science Funded by the National Heart, Lung, and Blood Institute”, delves into the type of data science research funded by NHLBI between fiscal year 2008 and fiscal year 2017. They identified 630 data science focused grants, funded by NHLBI, using keywords for bioinformatics and computational biology. They then analyzed the distribution of these grants across different disease areas and compared the results to data science grants funded by other NIH institutes or centers. Around 64% of funded grants were for cardiovascular disease with 22% in lung and airway disease, 12% in blood disease and 2% in sleep. NHLBI's investment in data science research grants averaged about 1% of its overall research grant investment, and this remained constant over the 10-year period. However, this proportion does not include other large scale investment by NHLBI in building data science platforms through other mechanisms. Of relevance to our listeners across all institutes, most funded data science research grants were related to genomics and other omics data. In this paper they include lots of graphs breaking down grant distributions across different categories, so it's worth a look as you plan your next grant application. That's all for December and the final episode of 2019. Thanks for listening and happy holidays to all who celebrate. I'm excited to be back in 2020, to kick off the next decade of exciting advances in genomic and precision cardiovascular medicine. This podcast was brought to you by Circulation: Genomic and Precision Medicine, and the American Heart Association Council on Genomic and Precision Medicine. This program is copyright American Heart Association 2019.

3. 

   4 Dec 2019

   34 November 2019

   Jane Ferguson:                  Hi there. Welcome to the November 2019 issue of Getting Personal: Omics of the Heart. I'm Jane Ferguson. This is your podcast from Circulation: Genomic and Precision Medicine. Let's get started. First up from Eric Curruth, Christopher Haggerty and colleagues from Geisinger, we have a paper entitled, “Prevalence and Electronic Health Record-based Phenotype of Loss-of-function Genetic Variance in Arrhythmogenic Right Ventricular Cardiomyopathy-associated Genes”. In this study, the team set out to understand the phenotypic consequences of variants and desmosome genes which has been associated with a arrhythmogenic right ventricular cardiomyopathy or ARVC. In clinical genetic testing, secondary findings of pathogenic or likely pathogenic variants in desmosome genes are recommended for clinical reporting. However, relatively little is known about the phenotypic consequences of these variants in a general clinical population. The team obtained whole exome sequencing data for over 61,000 individuals from the DiscovEHR cohort, part of the Geisinger MyCode Community Health Initiative. They then screened individuals for a putative loss of function variants in PKP2, DSC2, DSG2, and DSP. They evaluated ARVC diagnostic criteria using previously conducted ECG and echocardiograms and performed a phenom-wide association study or PHeWAS using EHR derived phenotypes. They found 140 people with an ARVC variant in one of the four genes, none of whom had an existing diagnosis of ARVC in the EHR. Further, there were no measurable differences in their ECG or echocardiogram findings compared with matched controls. There were also no associations with any heart disease phenotypes as assessed by PHeWAS. Overall, they report a prevalence of ARVC loss of function variants of around one in 435 in a general clinical population of predominantly European descent, but they did not find evidence that these variants associated with specific phenotypes. Thus, the clinical relevance of putative loss of function variants in desmosome genes still remains to be determined. The next paper is titled, “MRAS Variants Cause Cardiomyocyte Hypertrophy in Patients-specific iPSC-derived Cardiomyocytes”. Additional evidence for MRS as a definitive Noonan syndrome susceptibility gene. This comes from Erin Higgins, Michael Ackerman, and colleagues from the Mayo Clinic. They were interested in understanding whether a recently identified Noonan syndrome variant in the MRS gene was necessary and sufficient to cause Noonan syndrome with cardiac hypertrophy. They generated induced pluripotent STEM cell or IPS C lines from patient derived cells carrying the glycine 23 veiling variant and MRS. In addition to isogenic control cells where the pathogenic variant was corrected back to wild-type using CRISPR CAS nine gene editing, they also created a disease model cell line by introducing the MRS variant into unrelated control cells. They then comprehensively characterized the phenotypes of the three cell lines using a variety of approaches including microscopy, immunofluorescence, single cell RNA seek, Western blot, qPCR, and live cell calcium imaging. Both the patient derived and the disease model IPS cardiomyocytes were larger than control cells and demonstrated changes in gene expression and intracellular pathway signaling characteristic of cardiac hypertrophy. The patient and disease model cells also displayed impaired calcium handling. Through in-vitro phenotyping, the team was able to demonstrate that the glycine 23 veiling MRS variant elicits a cardiac hypertrophy phenotype and IPSC cardiomyocytes, that strongly suggests that this variant is responsible for the observed Noonan syndrome associated cardiac hypertrophy in the effected patients. Next up is a review from Christopher Lee, Iftikhar Kullo, and colleagues also from the Mayo Clinic on “New Case Detection by Cascade Testing in Familial Hypercholesterolemia: A Systematic Review of the Literature”. In this review they set out to systematically assess cascade testing programs for familial hypercholesterolemia, a disease which has a prevalence of about one and 250 but is estimated to be diagnosed in under 10% of patients. They identified published studies across the world which had conducted cascade testing and had reported the number of index cases and number of relatives tested and had also specified their methods of contacting relatives and testing. Using these criteria, they identified 10 studies for inclusion spanning several European countries, South Africa, New Zealand, Australia, and Brazil. The team calculated the proportion of relatives testing positive and the number of new cases per index case to facilitate comparison between studies. The mean number of programs was 242 with an average of 826 relatives per study. The average yield was 45%, ranging from 30 to 60%. the mean new cases per index case was 1.65 with a range of 0.22 to 8.0. Studies that use direct contact versus indirect contact for relatives and those that tested beyond first degree relatives had a greater yield. Further, active sample collection versus collection at clinic and using genetic testing versus biochemical testing was similarly associated with a higher yield. Despite differences between the United States and other countries, applying these strategies when establishing new cascade testing programs in the US may help promote success of these programs. Our next paper concerns “Randomization of Left-right Asymmetry and Congenital Heart Defects: The Role of DNAH5 in Humans and Mice”. And this was conducted by Tabea Nöthe-Menchen, Heymut Omran, and colleagues from University Children's Hospital Muenster and the PCD study group. They were interested in understanding the relationship between congenital heart defects and laterality defects where internal organs are atypically positioned, such as in a mirror image as occurs in situs inversus. Ciliary dyskinesia is thought to play a role in situs inversus and the most frequently mutated gene in primary ciliary dyskinesia is DNAH5. The team does hypothesize that DNAH5 mutations may play a role in congenital heart disease. They characterized phenotypes in 132 patients with primary ciliary dyskinesia carrying disease causing DNAH5 mutations and also studied left right access establishment using a DNAH5 mutant mouse model. 66% of patients in their study had laterality defects, 88% of whom presented with situs inversus totalis and 6% presented with congenital heart disease. In the mass model, they observed immotile cilia, impaired flow with the left right organizer and randomization of nodal signaling with normal reversed or bilateral expression of key molecules. Their study thus demonstrates that mutation of DNAH5 is associated with congenital heart defects and they further highlight the ciliary mechanisms underlying defects and development of left right positioning during embryogenesis. Consideration of celiopathy related symptoms may be warranted when examining patients with congenital heart defects. Next up, we have a research letter from William Goodyear, Marco Perez and colleagues from Stanford University on “Broad Genetic Testing in a Clinical Setting Uncovers a High Prevalence of Titan Loss-of-Function Variants in Very Early-Onset Atrial Fibrillation”. They were interested in understanding genetic determinants of atrial fibrillation and hypothesized that causal genetic variants would be enriched in individuals with very early onset AF, who are diagnosed with AF under the age of 45 with no other significant comorbidities. They identified 25 families comprising 23 unrelated patients with very early onset AF who had been evaluated and received genetic counseling at Stanford between 2014 and 2018. The mean age of AF diagnosis was 27.2 years and 76% of patients were male. 40% of patients had a first or second degree relative with very early onset AF, while 36% at first or second degree relatives with either early onset idiopathic cardiomyopathy, unexplained sudden death or strokes. 85% of patients were identified as having at least one rare variant in a cardiomyopathy associated gene. Six patients carried actionable pathogenic or likely pathogenic variants, four of which were in the titan gene. A subset of individuals were further evaluated by MRI or computed tomography on average 817 days after their first presentation and this revealed high rates of cardiac abnormalities including reduced ventricular function, chamber enlargement, borderline LV non compaction, or late gadolinium enhancement. These were not noted on echocardiogram at presentation, suggesting there may have been subsequent disease development or progression. Overall, this study highlights a high rate of familial disease and implicates an association between very early onset AF and rare variants in titan before the clinical onset of cardiomyopathy. The final letter this month comes from Yu Xia, Shaoxian Chen, Ping Li, Jian Zhuang and colleagues from Guangdong Academy of Medical Sciences and is entitled, “A Novel Mutation in MYH6 in Two Unrelated Chinese Han Families with Familial Atrial Septal Defect”. They report on two unrelated families who presented with secundum atrial septal defect or ASD2. Whole exome sequencing revealed a novel variant and the MYH6 gene in both families, with the same variant present in all effected individuals but not in unaffected family members or unrelated controls. Because other variants in MYH6 have been reported to effect myofibril formation. The team studied the effect of the novel variant on the myofibrillar organization through transient transfection of CTC 12 cells. The MYH6 E526K variant was associated with a reduced striated I pattern and increased non-striated patterning. There was no effect on ATPase activity. Protein modeling suggested a variant of the effective position would reduce hydrogen bonding between alpha helices in the actin interface two region, increasing the volume of the cavity between the alpha helices and promoting the exposure of the alkaline side chain in the actin binding region. This could impair the interaction between the myosin motor head and actin. What these data suggests are that this novel MYH6 heterozygous variant may underlie ASD2 in two unrelated Chinese Han families by impairing myofibrillar organization. That's all for November 2019. Thank you for listening and I look forward to being back in December for the final episode of 2019. This podcast was brought to you by Circulation: Genomic and Precision Medicine and the American Heart Association council on genomic and precision medicine. This program is copyright American Heart Association 2019.

Reach and audience

Public platform figures. Ratings count people who left a rating, not total listeners.

Apple Podcasts (US)

5.0 / 5

2 ratings

Contact Getting Personal: Omics of the Heart

Guest appearances

Books guests

Based on episode analysis; this does not confirm that the show is currently accepting guests.