Additional Genetic Variants in Inherited Dilated Cardiomyopathy: Just Another Brick in the Wall? [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 16, 2018 Category: Cardiology Authors: van Tintelen, J. P., Pinto, Y. M. Tags: Genetics, Cardiomyopathy, Heart Failure Editorial Source Type: research

Multigenic Disease and Bilineal Inheritance in Dilated Cardiomyopathy Is Illustrated in Nonsegregating LMNA Pedigrees [Original Articles]
Conclusions: Our data support DCM as a genetically heterogeneous disease with, at times, multigene causation. Although the frequency of DCM resulting from multigenic cause is uncertain, our data suggest it may be higher than previously anticipated. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 16, 2018 Category: Cardiology Authors: Cowan, J. R., Kinnamon, D. D., Morales, A., Salyer, L., Nickerson, D. A., Hershberger, R. E. Tags: Genetics, Cardiomyopathy, Heart Failure Original Articles Source Type: research

Rare and Low-Frequency Variant of ARHGEF17 Is Associated With Intracranial Aneurysms [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 11, 2018 Category: Cardiology Authors: He, L., Pierce, R. W., Min, W. Tags: Genetic, Association Studies, Cerebral Aneurysm Editorial Source Type: research

PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) Status and Protection Against Ischemic Stroke: PheWAS, TreWAS, and More [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 11, 2018 Category: Cardiology Authors: Sullivan, D., Bonnitcha, P., Spinks, C., Keech, T. Tags: Cardiovascular Disease, Diabetes, Type 2, Genetic, Association Studies, Ischemic Stroke Editorial Source Type: research

Managing Secondary Genomic Findings Associated With Arrhythmogenic Right Ventricular Cardiomyopathy: Case Studies and Proposal for Clinical Surveillance [Perspective]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 11, 2018 Category: Cardiology Authors: Haggerty, C. M., Murray, B., Tichnell, C., Judge, D. P., Tandri, H., Schwartz, M., Sturm, A. C., Matsumura, M. E., Murray, M. F., Calkins, H., Fornwalt, B. K., James, C. A. Tags: Arrhythmias, Risk Factors, Genetics, Cardiomyopathy Perspective Source Type: research

Large-Scale Phenome-Wide Association Study of PCSK9 Variants Demonstrates Protection Against Ischemic Stroke [Original Articles]
Conclusions: This result represents the first genetic evidence in a large cohort for the protective effect of PCSK9 inhibition on ischemic stroke and corroborates exploratory evidence from clinical trials. PCSK9 inhibition was not associated with variables other than those related to LDL (low-density lipoprotein) cholesterol, atherosclerosis, and type 2 diabetes mellitus, suggesting that other effects are either small or absent. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 11, 2018 Category: Cardiology Authors: Rao, A. S., Lindholm, D., Rivas, M. A., Knowles, J. W., Montgomery, S. B., Ingelsson, E. Tags: Cardiovascular Disease, Diabetes, Type 2, Genetic, Association Studies, Ischemic Stroke Original Articles Source Type: research

Rho Guanine Nucleotide Exchange Factor ARHGEF17 Is a Risk Gene for Intracranial Aneurysms [Original Articles]
Conclusions: Our results provide compelling evidence that ARHGEF17 is a risk gene for IA. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 11, 2018 Category: Cardiology Authors: Yang, X., Li, J., Fang, Y., Zhang, Z., Jin, D., Chen, X., Zhao, Y., Li, M., Huan, L., Kent, T. A., Dong, J.-F., Jiang, R., Yang, S., Jin, L., Zhang, J., Zhong, T. P., Yu, F. Tags: Computational Biology, Basic Science Research, Genetics, Functional Genomics, Cerebral Aneurysm Original Articles Source Type: research

Response by Lee and Stouffer to Letter Regarding Article, "Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention" [Response to Letter to the Editor]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 9, 2018 Category: Cardiology Authors: Lee, C. R., Stouffer, G. A. Tags: Genetics, Pharmacology, Acute Coronary Syndromes, Atherosclerosis Response to Letter to the Editor Source Type: research

Letter by Aw et al Regarding Article, "Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention" [Letter to the Editor]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 9, 2018 Category: Cardiology Authors: Aw, J. W. X., Tan, D. S.-Y., Goh, L. L. Tags: Genetics, Percutaneous Coronary Intervention, Acute Coronary Syndromes Letter to the Editor Source Type: research

HCN4 Gene Polymorphisms and Tachycardia-Induced Cardiomyopathy: True or Spurious Association? [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 9, 2018 Category: Cardiology Authors: Tsai, C.-T. Tags: Basic Science Research Editorial Source Type: research

Multiplexed Targeted Resequencing Identifies Coding and Regulatory Variation Underlying Phenotypic Extremes of High-Density Lipoprotein Cholesterol in Humans [Original Articles]
Background: Genome-wide association studies have uncovered common variants at many loci influencing human complex traits, such as high-density lipoprotein cholesterol (HDL-C). However, the contribution of the identified genes is difficult to ascertain from current efforts interrogating common variants with small effects. Thus, there is a pressing need for scalable, cost-effective strategies for uncovering causal variants, many of which may be rare and noncoding. Methods: Here, we used a molecular inversion probe target capture approach to resequence both coding and regulatory regions at 7 HDL-C–associated loci in 79...
Source: Circulation: Cardiovascular Genetics - July 9, 2018 Category: Cardiology Authors: Khetarpal, S. A., Babb, P. L., Zhao, W., Hancock-Cerutti, W. F., Brown, C. D., Rader, D. J., Voight, B. F. Tags: Basic Science Research, Gene Expression & Regulation, Genetic, Association Studies, Genetics, Functional Genomics Original Articles Source Type: research

HCN4 Gene Polymorphisms Are Associated With Occurrence of Tachycardia-Induced Cardiomyopathy in Patients With Atrial Fibrillation [Original Articles]
Conclusions: The HCN4 gene single-nucleotide polymorphism rs7164883 may be a new genetic marker for TIC in patients with AF. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - July 9, 2018 Category: Cardiology Authors: Nakano, Y., Ochi, H., Sairaku, A., Onohara, Y., Tokuyama, T., Motoda, C., Matsumura, H., Tomomori, S., Amioka, M., Hironobe, N., Ohkubo, Y., Okamura, S., Makita, N., Yoshida, Y., Chayama, K., Kihara, Y. Tags: Atrial Fibrillation, Genetics, Cardiomyopathy Original Articles Source Type: research

Clonal Hematopoiesis: Somatic Mutations in Blood Cells and Atherosclerosis [Review]
The most important prognostic factor for atherosclerotic cardiovascular disease is age, independent of all other recognized risk factors. Recently, exome sequence analyses showed that somatic mutations in blood cells, a process termed clonal hematopoiesis, are common and increase in prevalence with age, with at least 1 in 10 adults older than 70 years affected. Carriers of clonal hematopoiesis have been shown to be not only at heightened risk for hematologic malignancy but also at increased risk for atherosclerotic cardiovascular disease. Here, we review the prior literature of clonal selection and expansion of hematopoiet...
Source: Circulation: Cardiovascular Genetics - July 9, 2018 Category: Cardiology Authors: Natarajan, P., Jaiswal, S., Kathiresan, S. Tags: Inflammation, Aging, Cardiovascular Disease, Genetics, Atherosclerosis Review Source Type: research

Branched-Chain Amino Acids: The Metabolic Link Between Type 2 Diabetes Mellitus and Cardiovascular Disease? [Correction]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 14, 2018 Category: Cardiology Tags: Correction Source Type: research

APOL1 Sends Its REGARDS to Cardiovascular Disease [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 13, 2018 Category: Cardiology Authors: Waitzman, J. S., Wilkins, J. T., Lin, J. Tags: Cardiovascular Disease, Genetic, Association Studies, Ischemic Stroke, Atherosclerosis, Coronary Artery Disease Editorial Source Type: research

APOL1 Nephropathy Risk Variants and Incident Cardiovascular Disease Events in Community-Dwelling Black Adults [Original Articles]
Conclusions: APOL1 high-risk status is associated with CVD events in community-dwelling Black adults without diabetes mellitus. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 13, 2018 Category: Cardiology Authors: Gutierrez, O. M., Irvin, M. R., Chaudhary, N. S., Cushman, M., Zakai, N. A., David, V. A., Limou, S., Pamir, N., Reiner, A. P., Naik, R. P., Sale, M. M., Safford, M. M., Hyacinth, H. I., Judd, S. E., Kopp, J. B., Winkler, C. A. Tags: Cardiovascular Disease, Race and Ethnicity, Risk Factors, Genetic, Association Studies, Ischemic Stroke Original Articles Source Type: research

Human Genetics of Obesity and Type 2 Diabetes Mellitus: Past, Present, and Future [Review]
Type 2 diabetes mellitus (T2D) and obesity already represent 2 of the most prominent risk factors for cardiovascular disease, and are destined to increase in importance given the global changes in lifestyle. Ten years have passed since the first round of genome-wide association studies for T2D and obesity. During this decade, we have witnessed remarkable developments in human genetics. We have graduated from the despair of candidate gene-based studies that generated few consistently replicated genotype-phenotype associations, to the excitement of an exponential harvest of loci robustly associated with medical outcomes thro...
Source: Circulation: Cardiovascular Genetics - June 13, 2018 Category: Cardiology Authors: Ingelsson, E., McCarthy, M. I. Tags: Diabetes, Type 2, Obesity, Genetic, Association Studies, Genetics, Functional Genomics Review Source Type: research

1986 American Heart Association Bugher Program Pivotal to Current Management and Research of Heart Disease [Perspective]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 6, 2018 Category: Cardiology Authors: Roberts, R. Tags: Cardiovascular Disease, Catheter-Based Coronary and Valvular Interventions, Coronary Artery Disease Perspective Source Type: research

Identification of Pathological FBN1 Variants Is Not Straightforward [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 6, 2018 Category: Cardiology Authors: West, M., Summers, K. Tags: Clinical Studies, Gene Expression & Regulation, Genetics Editorial Source Type: research

Low Birth Weight: A Novel Cardiovascular Risk Factor? [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 6, 2018 Category: Cardiology Authors: Laina, A., Stellos, K. Tags: Diabetes, Type 2, Epidemiology, Risk Factors, Genetic, Association Studies, Coronary Artery Disease Editorial Source Type: research

Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease: Addressing the Barker Hypothesis With Mendelian Randomization [Original Articles]
Conclusions: Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 6, 2018 Category: Cardiology Authors: Zanetti, D., Tikkanen, E., Gustafsson, S., Priest, J. R., Burgess, S., Ingelsson, E. Tags: Genetics Original Articles Source Type: research

Tailoring the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Guidelines for the Interpretation of Sequenced Variants in the FBN1 Gene for Marfan Syndrome: Proposal for a Disease- and Gene-Specific Guideline [Original Articles]
Conclusions: Our study shows that classification of variants remains challenging and may change over time. Currently, a higher level of evidence is necessary to classify a variant as pathogenic. Gene-specific guidelines may be useful to allow a more precise and uniform interpretation of the variants to accurately support clinical decision-making. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - June 6, 2018 Category: Cardiology Authors: Muino-Mosquera, L., Steijns, F., Audenaert, T., Meerschaut, I., De Paepe, A., Steyaert, W., Symoens, S., Coucke, P., Callewaert, B., Renard, M., De Backer, J. Tags: Genetics, Aneurysm, Aortic Dissection Original Articles Source Type: research

Looking for the Missing Links: Challenges in the Search for Genotype-Phenotype Correlation in Marfan Syndrome [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 30, 2018 Category: Cardiology Authors: De Backer, J., Campens, L., Muino Mosquera, L. Tags: Genetics, Aneurysm, Aortic Dissection Editorial Source Type: research

Variants of Uncertain Significance: Should We Revisit How They Are Evaluated and Disclosed? [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 30, 2018 Category: Cardiology Authors: Morales, A., Hershberger, R. E. Tags: Cardiovascular Disease, Risk Factors, Genetics, Ethics and Policy Editorial Source Type: research

Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome [Original Articles]
Background: Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between FBN1 genotype and severe aortopathy (aortic root replacement, type A dissections, and related death). Methods: We evaluated 248 patients with pathogenic or likely pathogenic FBN1 variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the FBN1 genotype on severe aortic events (aortic root replacement, type A dissections, and related death). RESULTS: The cum...
Source: Circulation: Cardiovascular Genetics - May 30, 2018 Category: Cardiology Authors: Takeda, N., Inuzuka, R., Maemura, S., Morita, H., Nawata, K., Fujita, D., Taniguchi, Y., Yamauchi, H., Yagi, H., Kato, M., Nishimura, H., Hirata, Y., Ikeda, Y., Kumagai, H., Amiya, E., Hara, H., Fujiwara, T., Akazawa, H., Suzuki, J.-i., Imai, Y., Nagai, R Tags: Genetic, Association Studies, Aneurysm, Aortic Dissection Original Articles Source Type: research

Ability of Patients to Distinguish Among Cardiac Genomic Variant Subclassifications [Original Articles]
Background: Clinical genetic testing for heritable cardiovascular disease has become a widely used tool to aid in the management of patients and their families. A 5-category variant classification system is commonly used for genetic test results, but some laboratories further subclassify variants of uncertain significance. How and whether patients perceive differences among the variant categories or subclassifications of variants of uncertain significance is unknown. Methods: We tested whether participants perceived differences in genetic variant subclassifications on outcomes including risk comprehension, risk perception...
Source: Circulation: Cardiovascular Genetics - May 30, 2018 Category: Cardiology Authors: Hellwig, L. D., Biesecker, B. B., Lewis, K. L., Biesecker, L. G., James, C. A., Klein, W. M. P. Tags: Cardiovascular Disease, Genetics, Diagnostic Testing, Behavioral/Psychosocial Treatment, Health Services Original Articles Source Type: research

Interdisciplinary Models for Research and Clinical Endeavors in Genomic Medicine: A Scientific Statement From the American Heart Association [AHA Scientific Statement]
The completion of the Human Genome Project has unleashed a wealth of human genomics information, but it remains unclear how best to implement this information for the benefit of patients. The standard approach of biomedical research, with researchers pursuing advances in knowledge in the laboratory and, separately, clinicians translating research findings into the clinic as much as decades later, will need to give way to new interdisciplinary models for research in genomic medicine. These models should include scientists and clinicians actively working as teams to study patients and populations recruited in clinical settin...
Source: Circulation: Cardiovascular Genetics - May 29, 2018 Category: Cardiology Authors: Musunuru, K., Arora, P., Cooke, J. P., Ferguson, J. F., Hershberger, R. E., Hickey, K. T., Lee, J.-M., Lima, J. A. C., Loscalzo, J., Pereira, N. L., Russell, M. W., Shah, S. H., Sheikh, F., Wang, T. J., MacRae, C. A., On behalf of the American Heart Assoc Tags: Statements and Guidelines AHA Scientific Statement Source Type: research

In This Issue: May [In This Issue: May]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 15, 2018 Category: Cardiology Tags: In This Issue: May Source Type: research

Response by Kapplinger et al to Letter Regarding Article, "Yield of the RYR2 Genetic Test in Suspected Catecholaminergic Polymorphic Ventricular Tachycardia and Implications for Test Interpretation" [Correspondence]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 11, 2018 Category: Cardiology Authors: Kapplinger, J. D., Tester, D. J., Ackerman, M. J. Tags: Arrhythmias, Sudden Cardiac Death, Genetics Correspondence Source Type: research

SCN10A-Dependent Late INa Current: Never Too Late for Cardiac Conduction? [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 11, 2018 Category: Cardiology Authors: Maier, L. S., Sossalla, S., Schulze-Bahr, E. Tags: Arrhythmias, Electrophysiology, Ion Channels/Membrane Transport Editorial Source Type: research

Letter by Ruiz-Guerrero et al Regarding Article, "Yield of the RYR2 Genetic Test in Suspected Catecholaminergic Polymorphic Ventricular Tachycardia and Implications for Test Interpretation" [Correspondence]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 11, 2018 Category: Cardiology Authors: Ruiz-Guerrero, L., Larranaga-Moreira, J. M., Barriales-Villa, R. Tags: Genetics Correspondence Source Type: research

Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction [Original Articles]
Conclusions: Our findings suggest an association between genetic variation in SCN10A, the late sodium current, and alterations in cardiac conduction. (Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 11, 2018 Category: Cardiology Authors: Macri, V., Brody, J. A., Arking, D. E., Hucker, W. J., Yin, X., Lin, H., Mills, R. W., Sinner, M. F., Lubitz, S. A., Liu, C.-T., Morrison, A. C., Alonso, A., Li, N., Fedorov, V. V., Janssen, P. M., Bis, J. C., Heckbert, S. R., Dolmatova, E. V., Lumley, T. Tags: Electrophysiology, Atrial Fibrillation, Ion Channels/Membrane Transport, Functional Genomics Original Articles Source Type: research

Frameshifts in Code and in Care: The Importance of Timely Genetic Evaluation [Perspective]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Reza, N., Chowns, J. L., Merrill, S. L., Marzolf, A., Zado, E. S., Palmer, M. B., Deshpande, C., Pryma, D. A., Rame, J. E., Marchlinski, F. E., Owens, A. T. Tags: Arrhythmias, Genetics, Cardiomyopathy, Nuclear Cardiology and PET, Transplantation Perspective Source Type: research

Genetic Regulation of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Plasma Levels: Another Piece of the Puzzle [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Paquette, M., Baass, A. Tags: Genetic, Association Studies, Atherosclerosis, Coronary Artery Disease Editorial Source Type: research

Genetic Variation and the Electrocardiograph: From Genome-Wide Association Studies to the Patient [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Hedley, P. L., Hagen, C. M., Christiansen, M. Tags: Cardiovascular Disease, Genetic, Association Studies, Functional Genomics, Electrocardiology (ECG), Meta Analysis Editorial Source Type: research

TRPM4 Mutation in Patients With Ventricular Noncompaction and Cardiac Conduction Disease [Clinical Vignettes]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Saito, Y., Nakamura, K., Nishi, N., Igawa, O., Yoshida, M., Miyoshi, T., Watanabe, A., Morita, H., Ito, H. Tags: Genetics Clinical Vignettes Source Type: research

Increased Prevalence of Congenital Heart Disease in Children With Diamond Blackfan Anemia Suggests Unrecognized Diamond Blackfan Anemia as a Cause of Congenital Heart Disease in the General Population: A Report of the Diamond Blackfan Anemia Registry [Research Letter]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Vlachos, A., Osorio, D. S., Atsidaftos, E., Kang, J., Lababidi, M. L., Seiden, H. S., Gruber, D., Glader, B. E., Onel, K., Farrar, J. E., Bodine, D. M., Aspesi, A., Dianzani, I., Ramenghi, U., Ellis, S. R., Lipton, J. M. Tags: Clinical Studies, Genetics, Congenital Heart Disease Research Letter Source Type: research

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval [Original Articles]
We examined both common and rare variants associated with the PR interval. Results: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Lin, H., van Setten, J., Smith, A. V., Bihlmeyer, N. A., Warren, H. R., Brody, J. A., Radmanesh, F., Hall, L., Grarup, N., Muller-Nurasyid, M., Boutin, T., Verweij, N., Lin, H. J., Li-Gao, R., van den Berg, M. E., Marten, J., Weiss, S., Prins, B. P., Haes Tags: Electrophysiology, Epidemiology, Genetic, Association Studies Original Articles Source Type: research

Genetic Regulation of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Plasma Levels and Its Impact on Atherosclerotic Vascular Disease Phenotypes [Original Articles]
Background: Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is a novel strategy to treat hypercholesterolemia and reduce cardiovascular events. However, the potential role of circulating plasma PCSK9 concentrations as a diagnostic and predictive biomarker remains uncertain as of now. Here, we aimed to identify genetic variants associated with plasma PCSK9 and investigate possible causal effects on atherosclerotic vascular disease phenotypes. Methods: We performed the first genome-wide association study of plasma PCSK9 levels in a cohort of suspected and confirmed coronary artery disease (LIFE-Heart; n=...
Source: Circulation: Cardiovascular Genetics - May 10, 2018 Category: Cardiology Authors: Pott, J., Schlegel, V., Teren, A., Horn, K., Kirsten, H., Bluecher, C., Kratzsch, J., Loeffler, M., Thiery, J., Burkhardt, R., Scholz, M. Tags: Lipids and Cholesterol, Genetic, Association Studies, Atherosclerosis Original Articles Source Type: research

Predicting Penetrance of SCN5A Rare Variants: Peering Beyond the Black and White and Into the Shades of Grey [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 4, 2018 Category: Cardiology Authors: Roberts, J. D. Tags: Arrhythmias, Electrophysiology, Sudden Cardiac Death, Genetics Editorial Source Type: research

Letter by Vermeer et al Regarding Article, "Phenotypic Spectrum of HCN4 Mutations: A Clinical Case" [Letter to the Editor]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 4, 2018 Category: Cardiology Authors: Vermeer, A. M. C., Christiaans, I., Lodder, E. M. Tags: Genetics Letter to the Editor Source Type: research

Application of Genetic Epidemiology to CETP (Cholesteryl Ester Transfer Protein) Concentration and Risk of Cardiovascular Disease [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - May 4, 2018 Category: Cardiology Authors: Merriman, T. R. Tags: Etiology, Lipids and Cholesterol, Epidemiology, Genetic, Association Studies, Chronic Ischemic Heart Disease Editorial Source Type: research

SCN5A (NaV1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance [Original Articles]
Background: Accurately predicting the impact of rare nonsynonymous variants on disease risk is an important goal in precision medicine. Variants in the cardiac sodium channel SCN5A (protein NaV1.5; voltage-dependent cardiac Na+ channel) are associated with multiple arrhythmia disorders, including Brugada syndrome and long QT syndrome. Rare SCN5A variants also occur in 1% of unaffected individuals. We hypothesized that in vitro electrophysiological functional parameters explain a statistically significant portion of the variability in disease penetrance. Methods: From a comprehensive literature review, we quantified the nu...
Source: Circulation: Cardiovascular Genetics - May 4, 2018 Category: Cardiology Authors: Kroncke, B. M., Glazer, A. M., Smith, D. K., Blume, J. D., Roden, D. M. Tags: Arrhythmias, Electrophysiology, Ion Channels/Membrane Transport, Genetics Original Articles Source Type: research

CETP (Cholesteryl Ester Transfer Protein) Concentration: A Genome-Wide Association Study Followed by Mendelian Randomization on Coronary Artery Disease [Original Articles]
Background: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. Methods: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium). RESULTS: In the discovery analysis...
Source: Circulation: Cardiovascular Genetics - May 4, 2018 Category: Cardiology Authors: Blauw, L. L., Li-Gao, R., Noordam, R., de Mutsert, R., Trompet, S., Berbee, J. F. P., Wang, Y., van Klinken, J. B., Christen, T., van Heemst, D., Mook-Kanamori, D. O., Rosendaal, F. R., Jukema, J. W., Rensen, P. C. N., Willems van Dijk, K. Tags: Lipids and Cholesterol, Cardiovascular Disease, Genetic, Association Studies, Genetics Original Articles Source Type: research

In This Issue: April [In This Issue: April]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - April 16, 2018 Category: Cardiology Tags: In This Issue: April Source Type: research

Family Matters: Outcomes of Hypertrophic Cardiomyopathy Family Screening [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - April 16, 2018 Category: Cardiology Authors: Ingles, J., Semsarian, C. Tags: Genetics, Cardiomyopathy, Hypertrophy Editorial Source Type: research

Outcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy [Original Articles]
Background: Contemporary hypertrophic cardiomyopathy (HCM) family screening includes clinical evaluation and genetic testing (GT). This screening strategy requires the identification of a pathogenic mutation in the proband. Our aim was to examine the results of this HCM screening strategy. Methods: Between 1985 and 2016, 777 relatives of 209 probands were assessed in the context of HCM screening. Genotype-positive (G+) relatives and relatives without genetic testing (GT) underwent repeated clinical evaluations. In genotype-negative (G-) relatives mortality was assessed during follow-up. Results: A pathogenic mutation was...
Source: Circulation: Cardiovascular Genetics - April 16, 2018 Category: Cardiology Authors: van Velzen, H. G., Schinkel, A. F. L., Baart, S. J., Oldenburg, R. A., Frohn-Mulder, I. M. E., van Slegtenhorst, M. A., Michels, M. Tags: Clinical Studies, Genetics, Cardiomyopathy, Hypertrophy, Mortality/Survival Original Articles Source Type: research

Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the National Investment in Genomic Research [White Paper]
The National Institutes of Health have made substantial investments in genomic studies and technologies to identify DNA sequence variants associated with human disease phenotypes. The National Heart, Lung, and Blood Institute has been at the forefront of these commitments to ascertain genetic variation associated with heart, lung, blood, and sleep diseases and related clinical traits. Genome-wide association studies, exome- and genome-sequencing studies, and exome-genotyping studies of the National Heart, Lung, and Blood Institute–funded epidemiological and clinical case–control studies are identifying large nu...
Source: Circulation: Cardiovascular Genetics - April 13, 2018 Category: Cardiology Authors: Musunuru, K., Bernstein, D., Cole, F. S., Khokha, M. K., Lee, F. S., Lin, S., McDonald, T. V., Moskowitz, I. P., Quertermous, T., Sankaran, V. G., Schwartz, D. A., Silverman, E. K., Zhou, X., Hasan, A. A. K., Luo, X.-z. J. Tags: Gene Expression & Regulation, Genetic, Association Studies, Genetically Altered and Transgenic Models, Genetics, Functional Genomics White Paper Source Type: research

Branched-Chain Amino Acids: The Metabolic Link Between Type 2 Diabetes Mellitus and Cardiovascular Disease? [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - April 12, 2018 Category: Cardiology Authors: Tuteja, S. Tags: Cardiovascular Disease, Diabetes, Type 2, Epidemiology, Risk Factors, Women Editorial Source Type: research

Genetics of Spontaneous Coronary Artery Dissection Gains New Momentum [Editorial]
(Source: Circulation: Cardiovascular Genetics)
Source: Circulation: Cardiovascular Genetics - April 12, 2018 Category: Cardiology Authors: Grond-Ginsbach, C., Engelter, S. T. Tags: Genetics, Acute Coronary Syndromes Editorial Source Type: research