Review
Genetics & Heredity
Muzamil Khawaja, Rehma Siddiqui, Salim S. Virani, Christopher I. Amos, Dhrubajyoti Bandyopadhyay, Hafeez Ul Hassan Virk, Mahboob Alam, Hani Jneid, Chayakrit Krittanawong
Summary: Acute myocardial infarction is a major contributor to global mortality, with a growing burden. The complex pathophysiology involves various acquired and inherited risk factors. As technology and medical therapy advance, the role of genetics in the development and management of myocardial infarction is increasingly recognized. Genomic studies have expanded the understanding of genetic determinants and the potential for personalized medicine and improved treatment strategies. This article reviews relevant genes and provides updates on gene-guided risk stratification and treatment strategies for acute myocardial infarction.
Review
Cell Biology
Shahood Fazal, Malik Bisserier, Lahouaria Hadri
Summary: PAH is a rare and chronic lung disease characterized by occlusion of small pulmonary arteries, leading to increased pulmonary vascular resistance and right ventricular pressure overload. Advances in multi-omics approaches and high-throughput sequencing have helped identify genetic variants in PAH patients, contributing to precision medicine and the development of gene-editing technologies and gene therapies as alternative approaches to treating genetic disorders in PAH.
Article
Cardiac & Cardiovascular Systems
Ana Morales, Jessica Goehringer, Despina Sanoudou
Summary: In the era of Precision Medicine, the approach to disease diagnosis, treatment, and prevention, including in Cardiology, is being transformed by genomics approaches. The American Heart Association emphasizes the importance of genetic counseling in delivering quality cardiovascular genetics care. With the increasing number and complexity of cardiogenetic tests, there is a need for specialized cardiovascular genetic counselors. Advanced training, along with online services, telemedicine, and patient-facing digital tools, are crucial for providing effective care. The timely implementation of these reforms is essential for translating scientific advancements into measurable benefits for patients with heritable cardiovascular disease and their families.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Medicine, General & Internal
Hiu Yee Heidi Cheng, Judy F. C. Chow, Kevin K. W. Lam, Shui Fan Lai, William Shu Biu Yeung, Ernest H. Y. Ng
Summary: This study aims to compare the efficacy in embryo selection based on morphology alone compared with non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and morphology in infertile women undergoing IVF. It is a randomised double-blind controlled trial conducted in two tertiary assisted reproduction centres with a total of 500 participants. The primary outcome is a live birth per the first embryo transfer.
Article
Cardiac & Cardiovascular Systems
Christopher Semsarian, Jodie Ingles, Samantha Barratt Ross, Sally L. Dunwoodie, Richard D. Bagnall, Jason C. Kovacic
Summary: Rapid advancements in understanding the genetic basis of cardiovascular diseases have ushered in the era of precision medicine, involving improved diagnostics, family screening, and targeted therapeutics. Future endeavors include polygenic risk scores and genome editing approaches for effective disease treatment.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Medicine, General & Internal
Christopher Duane Rugg, Till Malzacher, Julia Ausserer, Andrea Rederlechner, Peter Paal, Mathias Strohle
Summary: This study reveals that male snowboarders are more prone to shoulder and chest injuries, often involved in accidents on challenging slopes and under the influence of alcohol, while female snowboarders are more likely to sustain back and pelvic injuries, with most injuries occurring on easier slopes.
Article
Biotechnology & Applied Microbiology
Agata Leonska-Duniec, Malgorzata Borczyk, Michal Korostynski, Myosotis Massidda, Ewelina Maculewicz, Pawel Cieszczyk
Summary: This study investigated the association between genetic variations in the MSTN, ACVR2A, and ACVR2B genes and athletic performance and competition level in the Polish population. The findings suggest that specific genotypes of these genes are significantly associated with athletes' competition level, particularly in the mixed-sports athlete group.
Review
Neurosciences
Giulia Straccia, Fabiana Colucci, Roberto Eleopra, Roberto Cilia
Summary: Understanding the pathophysiology and genetic background of Parkinson's disease is crucial for developing effective disease-modifying therapeutic strategies. The discovery of genetic variants causing or increasing the risk for PD has contributed to refining the classification of the disease and guiding the decision-making process on different therapies. However, the heterogeneity in molecular pathophysiology among PD populations may explain the disappointing results of current disease-modifying strategies. Personalized medicine should be prioritized in the future. This review discusses the current therapeutic options for PD and the challenges in successful clinical trials, as well as the role of genetics in guiding treatment decisions in daily clinical practice.
Review
Cardiac & Cardiovascular Systems
Clint L. Miller, Amy R. Kontorovich, Ke Hao, Lijiang Ma, Conrad Iyegbe, Johan L. M. Bjorkegren, Jason C. Kovacic
Summary: Atherosclerosis is the most common vascular disease worldwide, while Mendelian vascular diseases are caused by single genetic changes. These two types of diseases have very different genetic bases, thus requiring different precision medicine approaches for treatment.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Review
Cell Biology
Dangtong Shang, Lingling Wang, Daniel J. Klionsky, Hanhua Cheng, Rongjia Zhou
Summary: Nearly all diseases in humans show sex differences to some extent, with autophagy playing a crucial role in diseases like cancer, neurodegeneration, and cardiovascular diseases. Although the molecular mechanisms of sex differences in autophagy are still largely unexplored, understanding the impact of sex differences on diseases can advance precision medicine.
Article
Cardiac & Cardiovascular Systems
Silvia G. Priori, Andrea Mazzanti, Demetrio J. Santiago, Deni Kukavica, Alessandro Trancuccio, Jason C. Kovacic
Summary: This article focuses on the precision medicine opportunities for catecholaminergic polymorphic ventricular tachycardia (CPVT), highlighting that CPVT can manifest as typical or atypical forms with different genetic changes and features, which is crucial for implementing personalized therapeutic approaches.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Daniel Seung Kim, Anna L. Gloyn, Joshua W. Knowles
Summary: Type 2 diabetes is highly prevalent and contributes to cardiovascular disease. Despite significant progress in identifying genetic variation associated with T2D risk, the promise of precision medicine has not been fully realized. Recent studies have identified sub-groups of individuals with differential risk for intermediate phenotypes, which could aid in patient stratification and bridging the gap towards precision medicine for T2D.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Toru Kubo, Hiroaki Kitaoka
Summary: Although many causative genes for primary cardiomyopathy have been identified, the use of genetic testing in routine practice is limited in Japan currently. Genetic diagnosis has been reported to be useful for early diagnosis through cascade genetic screening in the family, differentiating secondary cardiomyopathies, and predicting prognosis in some patients; nonetheless, the acquisition of genetic information for cardiomyopathy is stagnating in actual clinical practice. The importance of pathogenicity studies of identified variants is growing and establishing a database of variants in Japanese people is necessary for precision medicine in patients with cardiomyopathy and their relatives.
JOURNAL OF CARDIAC FAILURE
(2023)
Article
Medicine, General & Internal
Bahar Hassanmirzaei, Zohreh Haratian, Ali Ahmadzadeh Amiri, Amir Ahmadzadeh Amiri, Navid Moghadam
Summary: The study found that some symptomatic cases had negative PCR results but positive serological test results; recovered patients showed significantly higher levels of IgG antibodies. Although serological testing alone may not be sufficient for diagnosing COVID-19, the results are beneficial for the understanding and management of the disease.
POSTGRADUATE MEDICAL JOURNAL
(2022)
Review
Cell Biology
Ann-Kathrin Schalkamp, Nabila Rahman, Jimena Monzon-Sandoval, Cynthia Sandor
Summary: A major challenge in medical genomics is to understand the genetic contributions to different clinical symptoms and disorders. Deep phenotyping can help investigate disease mechanisms and risk factors, advancing precision medicine. Parkinson's disease, a neurodegenerative disorder, has diverse phenotypes with genetic heterogeneity, which can be addressed through deep phenotyping.
DISEASE MODELS & MECHANISMS
(2022)
Article
Clinical Neurology
Pauline E. Schneeberger, Fanny Kortum, Georg Christoph Korenke, Malik Alawi, Rene Santer, Mathias Woidy, Daniela Buhas, Stephanie Fox, Jane Juusola, Majid Alfadhel, Bryn D. Webb, Emanuele G. Coci, Rami Abou Jamra, Manuela Siekmeyer, Saskia Biskup, Corina Heller, Esther M. Maier, Poupak Javaher-Haghighi, Maria F. Bedeschi, Paola F. Ajmone, Maria Iascone, Hilde Peeters, Katleen Ballon, Jaak Jaeken, Aroa Rodriguez Alonso, Maria Palomares-Bralo, Fernando Santos-Simarro, Marije E. C. Meuwissen, Diane Beysen, R. Frank Kooy, Henry Houlden, David Murphy, Mohammad Doosti, Ehsan Karimiani, Majid Mojarrad, Reza Maroofian, Lenka Noskova, Stanislav Kmoch, Tomas Honzik, Heidi Cope, Amarilis Sanchez-Valle, Bruce D. Gelb, Ingo Kurth, Maja Hempel, Kerstin Kutsche
Review
Biochemistry & Molecular Biology
James A. Sanford, Christopher D. Nogiec, Malene E. Lindholm, Joshua N. Adkins, David Amar, Surendra Dasari, Jonelle K. Drugan, Facundo M. Fernandez, Shlomit Radom-Aizik, Simon Schenk, Michael P. Snyder, Russell P. Tracy, Patrick Vanderboom, Scott Trappe, Martin J. Walsh
Article
Genetics & Heredity
Megan H. Hawley, Naif Almontashiri, Leslie G. Biesecker, Natalie Berger, Wendy K. Chung, John Garcia, Theresa A. Grebe, Melissa A. Kelly, Matthew S. Lebo, Daniela Macaya, Hui Mei, Julia Platt, Gabi Richard, Ashley Ryan, Kate L. Thomson, Matteo Vatta, Roddy Walsh, James S. Ware, Matthew Wheeler, Hana Zouk, Heather Mason-Suares, Birgit Funke
Article
Genetics & Heredity
Kelly Schoch, Cecilia Esteves, Anna Bican, Rebecca Spillmann, Heidi Cope, Allyn McConkie-Rosell, Nicole Walley, Liliana Fernandez, Jennefer N. Kohler, Devon Bonner, Chloe Reuter, Nicholas Stong, John J. Mulvihill, Donna Novacic, Lynne Wolfe, Ayat Abdelbaki, Camilo Toro, Cyndi Tifft, May Malicdan, William Gahl, Pengfei Liu, John Newman, David B. Goldstein, Jason Hom, Jacinda Sampson, Matthew T. Wheeler, Joy Cogan, Jonathan A. Bernstein, David R. Adams, Alexa T. McCray, Vandana Shashi
Summary: The study evaluates the contributions of UDN clinical sites in diagnosing patients with undiagnosed diseases, demonstrating significant improvements in diagnosis rates and new disease gene discoveries.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Sacha Ferdinandusse, Kirsty McWalter, Heleen te Brinke, Lodewijk Ijlst, Petra M. Mooijer, Jos P. N. Ruiter, Alida E. M. van Lint, Mia Pras-Raves, Eric Wever, Francisca Millan, Maria J. Guillen Sacoto, Amber Begtrup, Mark Tarnopolsky, Lauren Brady, Roger L. Ladda, Susan L. Sell, Catherine B. Nowak, Jessica Douglas, Cuixia Tian, Elizabeth Ulm, Seth Perlman, Arlene V. Drack, Karen Chong, Nicole Martin, Jennifer Brault, Elly Brokamp, Camilo Toro, William A. Gahl, Ellen F. Macnamara, Lynne Wolfe, Quinten Waisfisz, Petra J. G. Zwijnenburg, Alban Ziegler, Magalie Barth, Rosemarie Smith, Sara Ellingwood, Deborah Gaebler-Spira, Somayeh Bakhtiari, Michael C. Kruer, Antoine H. C. van Kampen, Ronald J. A. Wanders, Hans R. Waterham, David Cassiman, Frederic M. Vaz
Summary: The study found that de novo variants affecting the Arg480 residue of FAR1 lead to an autosomal dominant disorder with a different disease mechanism than that of recessive FAR1 deficiency. FAR1 deficiency causes defective ether lipid synthesis, while the de novo variants result in elevated plasmalogen levels. Further functional studies in fibroblasts revealed disruption of plasmalogen-dependent feedback regulation of FAR1 protein levels.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Shilpa Nadimpalli Kobren, Dustin Baldridge, Matt Velinder, Joel B. Krier, Kimberly LeBlanc, Cecilia Esteves, Barbara N. Pusey, Stephan Zuchner, Elizabeth Blue, Hane Lee, Alden Huang, Lisa Bastarache, Anna Bican, Joy Cogan, Shruti Marwaha, Anna Alkelai, David R. Murdock, Pengfei Liu, Daniel J. Wegner, Alexander J. Paul, Shamil R. Sunyaev, Isaac S. Kohane
Summary: Genomic sequencing has become a powerful tool for discovering genetic abnormalities underlying rare Mendelian conditions. This study found that while well-established practices exist for initial steps in variant calling and quality control, there is substantial divergence in later stages for variant prioritization and multimodal data integration across different sites. The differences suggest that advancements in structural variant detection, noncoding variant interpretation, and integration of additional biomedical data could be especially promising for solving chronically undiagnosed cases.
GENETICS IN MEDICINE
(2021)
Article
Genetics & Heredity
Marc Jan Bonder, Craig Smail, Michael J. Gloudemans, Laure Fresard, David Jakubosky, Matteo D'Antonio, Xin Li, Nicole M. Ferraro, Ivan Carcamo-Orive, Bogdan Mirauta, Daniel D. Seaton, Na Cai, Dara Vakili, Danilo Horta, Chunli Zhao, Diane B. Zastrow, Devon E. Bonner, Matthew T. Wheeler, Helena Kilpinen, Joshua W. Knowles, Erin N. Smith, Kelly A. Frazer, Stephen B. Montgomery, Oliver Stegle
Summary: By integrating data from 1,367 human iPSC lines, researchers comprehensively mapped common and rare regulatory variants in human pluripotent cells, identified new colocalization events specific to iPSCs, and demonstrated the utility of iPSCs in identifying causal genes for rare diseases.
Article
Cardiac & Cardiovascular Systems
Megan J. Puckelwartz, Lorenzo L. Pesce, Lisa M. Dellefave-Castillo, Matthew T. Wheeler, Tess D. Pottinger, Avery C. Robinson, Samuel D. Kearns, Anthony M. Gacita, Zachary J. Schoppen, Wenyu Pan, Gene Kim, Jane E. Wilcox, Allen S. Anderson, Euan A. Ashley, Sharlene M. Day, Thomas Cappola, Gerald W. Dorn, Elizabeth M. McNally
Summary: By comparing protein coding variations in the genomes of familial cases of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), it was found that individuals with DCM had more nonsynonymous single-nucleotide variants (nsSNVs) in cardiomyopathy genes. These variants were significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter in individuals with DCM, but not in those with HCM. This suggests that increased variation in cardiomyopathy genes predisposes individuals to DCM and worsens disease severity.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Multidisciplinary Sciences
David Amar, Malene E. Lindholm, Jessica Norrbom, Matthew T. Wheeler, Manuel A. Rivas, Euan A. Ashley
Summary: This study explores the molecular mechanisms driving exercise adaptation by conducting a meta-analysis on human skeletal muscle, revealing time-specific patterns of acute and long-term exercise responses, as well as identifying sex- and age-specific changes.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Medicine, Research & Experimental
Stephen B. Montgomery, Jonathan A. Bernstein, Matthew T. Wheeler
Summary: This perspective summarizes recent developments and challenges in using RNA-seq for rare disease investigation, highlighting its ability to detect aberrant gene expression and alternative splicing as functional evidence. However, one major limitation is the specificity of gene expression and the difficulty in obtaining relevant tissue samples. Future advancements in computational methods and experimental techniques are expected to overcome these limitations and broaden the use of RNA sequencing in rare disease diagnosis and precision health.
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2022)
Article
Cardiac & Cardiovascular Systems
Anders Johnson, Steven G. Hershman, Ali Javed, C. Mikael Mattsson, Jeffrey Christle, Marily Oppezzo, Euan A. Ashley
Summary: Mobile health (mHealth) is a field that utilizes mobile technologies such as smartphones to provide healthcare support and interventions, with a broader reach than traditional healthcare networks. My Fitness Counts is a cross-platform mHealth study aimed at measuring cardiovascular fitness levels. Through a quality control process, over 70 bugs were identified and corrected.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Mark Hofmeyer, Garrie J. Haas, Elizabeth Jordan, Jinwen Cao, Evan Kransdorf, Gregory A. Ewald, Alanna A. Morris, Anjali Owens, Brian Lowes, Douglas Stoller, W. H. Wilson Tang, Sonia Garg, Barry H. Trachtenberg, Palak Shah, Salpy V. Pamboukian, Nancy K. Sweitzer, Matthew T. Wheeler, Jane E. Wilcox, Stuart Katz, Stephen Pan, Javier Jimenez, Frank Smart, Jessica Wang, Stephen S. Gottlieb, Daniel P. Judge, Charles K. Moore, Gordon S. Huggins, Daniel D. Kinnamon, Hanyu Ni, Ray E. Hershberger
Summary: Advanced dilated cardiomyopathy (DCM) is associated with a higher probability of pathogenic or likely pathogenic rare variants in DCM genes, which can help assess the risk of outcomes in managing DCM patients and their at-risk family members.
Article
Medicine, General & Internal
Elizabeth Jordan, Daniel D. Kinnamon, Garrie J. Haas, Mark Hofmeyer, Evan Kransdorf, Gregory A. Ewald, Alanna A. Morris, Anjali Owens, Brian Lowes, Douglas Stoller, W. H. Wilson Tang, Sonia Garg, Barry H. Trachtenberg, Palak Shah, Salpy V. Pamboukian, Nancy K. Sweitzer, Matthew T. Wheeler, Jane E. Wilcox, Stuart Katz, Stephen Pan, Javier Jimenez, Daniel P. Fishbein, Frank Smart, Jessica Wang, Stephen S. Gottlieb, Daniel P. Judge, Charles K. Moore, Jonathan O. Mead, Natalie Hurst, Jinwen Cao, Gordon S. Huggins, Jason Cowan, Hanyu Ni, Heidi L. Rehm, Gail P. Jarvik, Matteo Vatta, Wylie Burke, Ray E. Hershberger
Summary: This study compares the rare variant genetic architecture of dilated cardiomyopathy (DCM) among patients with DCM who are of African ancestry compared with European ancestry. The study found that African patients with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Cardiac & Cardiovascular Systems
Christoffer Rasmus Vissing, Anna Axelsson Raja, Sharlene M. Day, Mark W. Russell, Kenneth Zahka, Harry M. Lever, Alexandre C. Pereira, Steven D. Colan, Renee Margossian, Anne M. Murphy, Charles Canter, Richard G. Bach, Matthew T. Wheeler, Joseph W. Rossano, Anjali T. Owens, Lee Benson, Luisa Mestroni, Matthew R. G. Taylor, Amit R. Patel, Ivan Wilmot, Philip Thrush, Jonathan H. Soslow, Jason R. Becker, Christine E. Seidman, Neal K. Lakdawala, Allison L. Cirino, John J. V. Mcmurray, Calum A. Macrae, Scott D. Solomon, Henning Bundgaard, E. John Orav, Carolyn Y. Ho
Summary: This study explored the potential of valsartan to modify disease development in subclinical HCM and characterized the short-term phenotypic progression. The results showed that valsartan did not have a significant effect on cardiac remodeling and the progression of subclinical HCM was minimal. Nearly one-fifth of the patients developed clinically overt HCM, and the transition to disease was associated with baseline interventricular septum thickness and left atrial volume index. These findings emphasize the importance of longitudinal follow-up of sarcomere variant carriers and the need to improve understanding of factors that drive disease penetrance and progression.
Article
Genetics & Heredity
Courtney M. Studwell, Emily G. Kelley, Janet S. Sinsheimer, Christina G. S. Palmer, Kimberly LeBlanc
Summary: This study investigates genetic result communication in families with rare and undiagnosed conditions. It finds that parents are more willing to share genetic results with family members, while adult participants tend to communicate risk factors. Many respondents did not remember discussing with healthcare providers how or what to communicate about the results, highlighting the need for more effective counseling strategies.
JOURNAL OF GENETIC COUNSELING
(2021)
