Getting Personal: Omics Of The Heart

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

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 eig

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.         

Jane Ferguson:                Hello. Welcome to episode 33 of Getting Personal: Omics Of The Heart, your podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson. This episode is from October 2019. Let's get started.                                            First up is a paper from Sébastien Thériault, Yohan Bossé, Jean-Jacques Schott and colleagues from Laval University, Quebec and INSERM in Mont. They published on genetic association analyses, highlight IL6, ALPL and NAV1 as three new susceptibility genes underlying Calcific Aortic Valve Stenosis.                                            In this paper, they were interested in finding out whether they could identify novel susceptibility genes for Calcific Aortic Valve Stenosis, or CAVS, which is a severe and often fatal condition with limited treatment options other than surgical aortic valve replacement. They conducted a GWAS meta-analysis across four European ancestry cohorts comprising over 5,000 cases and over 354,000 controls. T

Jane Ferguson:                Hi, everyone. Welcome to Getting Personal: Omics of the Heart, the monthly 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 CircGen. This is episode 32 from September 2019. Starting off this month, we have a paper on Genetic Mosaicism in Calmodulinopathy brought to us by Lisa Wren, Alfred George and colleagues from Northwestern University. They were interested in exploring the disease phenotypes that result from variation in the calmodulin genes, CALM1, 2 and 3.                                            Mutations in calmodulin are known to associate with congenital arrhythmia, but the group hypothesized that there may be a broader range of phenotypes associated with calmodulin mutations. They report on four unrelated families all with pro bands exhibiting symptoms of prolonged QTC interval and documented ventricular arrhythmia. They conducted targete

Jane Ferguson:                Hello, and welcome to Getting Personal, Omics of the Heart, your monthly podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson. It is August, 2019, and this is episode 31. Let's get started.                                            Our first paper comes from Freyja van Lint and Cynthia James, from University Medical Center Utrecht, and is entitled Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmosomal Variants Are Rarely De Novo, Segregation and Haplotype Analysis of a Multinational Cohort. In this study, the team was interested in exploring variants that are associated with arrhythmogenic right ventricular cardiomyopathy or ARVC. ARVC is often attributable to pathogenic variants in genes encoding cardiac desmosomal proteins, but the origin of these variants had not been comprehensively studied.                                            The investigators identified ARVC probands meeting 2010 task force criteria from three ARVC registries

Jane Ferguson:                Hi everyone. Welcome to Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson and this is episode 30 from July 2019.                                            First up we have a paper, the Subtype Specificity of Genetic Loci Associated With Stroke in 16664 cases and 32792 Controls, from Matthew Trailer and colleagues on behalf of the NINDS Stroke Genetics Network and the International Stroke Genetics Consortium.                                            They were interested in understanding whether genetic loci previously found to be associated with stroke have distinct associations with stroke subtypes, specifically ischemic and hemorrhagic stroke. They compiled data sets through an international consortium to analyze 16664 stroke cases and 32792 controls, all of European ancestry. The cases were subtyped using two different stroke classification systems: the Trial of ORG 10172 in Acute Stroke Treatment, or TOAS

Jane Ferguson:                Hi, everyone. Welcome to episode 29 of Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson from Vanderbilt University Medical Center and an associate editor at Circ: Genomic and Precision Medicine. Let's dive in and see what's new in the June issue.                                            First up, Validation of Genome-Wide Polygenic Risk Scores for Coronary Artery Disease in French Canadians from Florian Wünnemann, Guillaume Lettre and colleagues from the University of Montreal. Polygenic scores have the potential to be used to predict disease risk, but have not been broadly validated in different populations. This team was interested in whether polygenic risk scores that have been found to predict coronary artery disease in European ancestry subjects in the UK Biobank would also predict disease in French Canadians. They calculated two different polygenic risk scores in over 3600 cases and over 7000 controls a

Jane Ferguson:  Hi, everyone. Welcome to Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. It's May 2019, and this is episode 28. So let's see what papers we have in the journal this month.                              First up, a paper from Mengyao Yu, Nabila Bouatia-Naji and colleagues from the Inserm Cardiovascular Research Center in Paris, entitled GWAS-Driven Gene-set Analyses, Genetic and Functional Follow-Up Suggest Glis1 as a Susceptibility Gene for Mitral Valve Prolapse.                              In this paper, they set out to characterize the genetic contributions to mitral valve prolapse, or MVP, to better understand the biological mechanisms underlying disease. They applied the gene-set enrichment analysis for QWAS tool and the pathway enrichment tool DEPICT to existing GWAS for MVP in a French sample to identify gene sets associated with MVP. They find significant enrichment of genes involved in pathways of relevance to valve biology and enri

Jane Ferguson:                Hello and welcome to Getting Personal: Omics of the Heart, your podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson from Vanderbilt University Medical Center, and this is episode 27 from April 2019.                                            This month, I talk to Riyaz Patel, the first author on not one, but two articles published this issue, presenting analyses from the GENIUS-CHD consortium. But before we get to the interview, let's review what else was published this month.                                            First up, we have a paper from Tamiel Turley, Timothy Olson and colleagues from the Mayo Clinic, entitled Rare Missense Variants in TLN1 Are Associated With Familial and Sporadic Spontaneous Coronary Artery Dissection. In this study, the authors were interested in identifying novel susceptibility genes for spontaneous coronary artery dissection or SCAD, which predominantly affects young women who appeared otherwise healthy. They conducted

Jane Ferguson:                Hello, and welcome to episode 26 of Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. I'm Jane Ferguson. It's March 2019, and I'm ready to spring into this month's papers, and apparently make really bad seasonal related jokes. Sorry all. Okay, let's get started.                                            First up, is a paper from Oren Akerborg, Rapolas Spalinskas, Sailendra Pradhananga, Pelin Sahlén and colleagues from the Royal Institute of Technology in Solna, Sweden entitled "High Resolution Regulatory Maps Connect Vascular Risk Variants to Disease Related Pathways." Their goal was to identify non-coding variants associated with coronary artery disease, particularly those with putative enhancers and to map these to changes in gene function. They generated genomic interaction maps using Hi-C chromosome confirmation capture, coupled with sequence capture in several cell types, including aortic and ethelial cells, smooth muscle c

Jane Ferguson:                Hi everybody. Welcome to Episode 25. I'm Jane Ferguson. This is Getting Personal: Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine, and it is February 2019. Let's get started.                                            The first paper this issue is a concurrent publication and comes to us from 29 different editors-in-chief of 27 major cardiovascular journals, led by Joseph Hill, editor-in-chief of Circulation. This editorial, entitled Medical Misinformation: Vet the Message! gives a pointed reminder of the real life risks of misinformation that spreads rapidly through social media and influences people who are making crucial decisions about healthcare for themselves and their families. Quoting directly from the paper they say, "We, the editors-in-chief of the major cardiovascular scientific journals around the globe, sound the alarm that human lives are at stake. People who decline to use a statin when recommended by their doctor, or parents who w

Jane Ferguson:  Hello, everyone. Welcome to Episode 23 of Getting Personal, Omics of the Heart, the podcast from Circulation: Genomic and Precision Medicine. It's December 2018. I'm Jane Ferguson. So let's get started.                              This month I talked to Dr. Merlin Butler from Kansas University Medical Center about an interesting clinical case he described recently in the Journal of Pediatric Genetics, concerning cardiac presentations in a case of classic Ehlers-Danlos syndrome with COL5A1 mutations.                              Keep listening for that interview, but first, let's talk about the papers in this month's issue of the Journal.                              Our first paper, entitled "Effects of Genetic Variance Associated With Familial Hypercholesterolemia on LDL Cholesterol Levels and Cardiovascular Outcomes in the Million Veteran Program." Comes from Yan Sun, Peter Wilson and co-authors on behalf of the V.A. Million Veterans Program. They were interested in the relatively betwee

Jane Ferguson:                Hello everyone, and happy new year. Welcome to episode 24 of Getting Personal: Omics of the Heart. It's January 2019, I am Jane Ferguson, an assistant professor at Vanderbilt University Medical Center and an associate editor at Circulation Genomic and Precision Medicine. We have a great line-up of papers this month in the journal, so let's jump right into the articles.                                            First up, a paper from Christopher Nelson, Nilesh Samani, and colleagues from the University of Lester entitled, "Genetic Assessment of Potential Long-Term On-Target Side Effects of PCSK9 Inhibitors."                                            I think most listeners are well aware of the efficacy of PCSK9 inhibition in reducing cardiovascular risk. However, as a relatively new treatment option, we do not yet have data on potential long-term side effects of PCSK9 inhibition. In this study, they utilized genetics as a proxy to understand potential long-term consequences of

Jane Ferguson:                Hello, welcome to Getting Personal: Omics of the Heart, Episode 22. This is a podcast from Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. I am Jane Ferguson and it's November 2018.                                            Our first article comes from Carlos Vanoye, Alfred George and colleagues from Northwestern University Feinberg School of Medicine and is entitled, High Throughput Functional Evaluation of KCNQ1 Decrypts Variance of Unknown Significance.                                            So a major growing problem in clinical genomics is that following the identification of a variant that is potentially linked to a disease phenotype, without further interrogation, it's really hard to make sense of the functional significance of that variant. Right now, the large number of variants of unknown significance lead to confusion for patients and clinicians alike. To allow for accurate diagnoses and the best treatment plan

Speaker 1:           Hi, everyone. Welcome to episode 21 of Getting Personal, Omics of the Heart from October 2018. I'm Jane Ferguson, an Assistant Professor at Vanderbilt University Medical Center and an Associate Editor at Circulation: Genomic and Precision Medicine. We have a great issue this month. So, let's dive straight in. First up, an article on "Loss-of-Function ABCC8 Mutations in Pulmonary Arterial Hypertension" from Michael Bohnen, Wendy Chung and colleagues from Columbia University. In pulmonary arterial hypertension, or PAH, compromised pulmonary arterial function can raise pressure in the pulmonary artery which leads to increased pulmonary vascular resistance. This ultimately results in right heart failure. While PAH is relatively rare, it has a high rate of mortality. Some genetic underpinnings have been identified, notably the KCNK3 gene identified by the same research group where they find that mutations result in potassium channelopathy. However, here the authors hypothesized that other gene

Jane Ferguson: Hi everyone. Welcome to episode 20 of Getting Personal Omics of the Heart, the podcast brought to you by the Circulation: Genomic and Precision Medicine Journal and the American Heart Association Council on Genomic and Precision Medicine. I'm Jane Ferguson from Vanderbilt University. It's September 2018 and let's dive straight into the papers from this month's issue of Circulation: Genomic and Precision Medicine.                                 We're starting off with some pharmacogenomics. Bruce Peyser, Deepak Voora and colleagues from Duke University published an article entitled, "Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings."                                 Although statins are generally well tolerated, 5-15% of patients taking statins for LDL lowering and cardiovascular protection end up developing statin associated muscular symptoms. Because onset of muscular symptoms associated with discontinuing statin use, as well as increas

Jane Ferguson: Hello. Welcome to episode 19 of Getting Personal: Omics of the Heart, the issue from August 2018. I am Jane Ferguson, and this podcast is brought to you by the Circulation: Genomic and Precision Medicine Journal and the American Heart Association Council on Genomic and Precision Medicine. Before I dive into the papers from this month, a reminder that early bird registration for AHA Scientific Sessions runs until September 4th, so go register now if you haven't already to take advantage of reduced rates. The meeting will be held in Chicago from November 10th through 12th, and it's the first year of the new three-day meeting format. It's already promising to be a really great meeting, and I'm hoping to see a lot of you there.     The August issue has a number of really interesting papers. First up, Gardar Sveinbjornsson, Eva Olafsdottir, Kari Stefansson, and colleagues from deCODE genetics-Amgen report that variants in NKX2-5 and FLNC cause dilated cardiomyopathy and sudden cardiac de

Jane:                                     Hi, everyone. Welcome to Episode 18 of Getting Personal: Omics of the Heart. I'm Jane Ferguson, and this podcast is brought to you by the Circulation: Genomic and Precision Medicine Journal and the American Heart Association Counsel on Genomic and Precision Medicine. It is July 2018, which means that the best possible place to be listening to this episode is at the beach, but failing that I can also recommend listening on planes, during your commute, while exercising or while drinking a nice cup of tea.                                                 So before I get into the papers we published this month, I want to ask for your help. If you're listening to this right now, hi, that means you, we're a year and a half into podcasting and I would love to know what content you like and where we could improve things. We have a poll up on Twitter this week, and I would really appreciate your input. If you're listening to this a little bit later and miss the active voting

Jane Ferguson:                 Hello, welcome to Getting Personal: Omics of the Heart. It is June 2018, and this is podcast episode 17. I'm Jane Ferguson, an assistant professor of medicine at Vanderbilt University Medical Center, and a proponent of precision medicine, genomics, and finding ways to prevent and treat heart disease. Jane Ferguson:                 This podcast is brought to you by Circulation: Genomic and Precision Medicine, and the AHA Council on Genomic and Precision Medicine. Jane Ferguson:                 For our interview this month, early career member, Jennie Lin talked to Beth McNally about science and careers in genomic medicine. We'll have more on that later but first I want to tell you about the cool papers we published in the journal this month. Jane Ferguson:                 First up, Orlando Gutierrez, Marguerite Irvin, Jeffrey Kopp, Cheryl Winkler, and colleagues from the University of Alabama at Birmingham, and the NIH, published an article entitled APOL1 Nephropathy Risk Variant