Article
Multidisciplinary Sciences
Yuanning Zheng, Francisco Carrillo-Perez, Marija Pizurica, Dieter Henrik Heiland, Olivier Gevaert
Summary: In this study, two deep learning models were used to predict the transcriptional subtypes and prognosis of glioblastoma (GBM) cells from histology images. The results showed consistent associations between spatial cellular organization and patient prognosis. The study also confirmed that transcriptional heterogeneity and cell-state plasticity are key factors in the development of therapeutic resistance in GBM.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Barbora Vitovcova, Veronika Skarkova, Radim Havelek, Jiri Soukup, Ananya Pande, Katerina Caltova, Emil Rudolf
Summary: In our study, we found that the repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of glioblastoma multiforme (GBM) cells. FLU affects microtubule structure and influences tubulins expression. Additionally, FLU decreases activation of STAT3 and leads to upregulation of p53 signaling pathway, resulting in cell cycle arrest and caspase-dependent cell death. These findings suggest FLU as a promising agent for GBM treatment.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Sana Munquad, Tapas Si, Saurav Mallik, Asim Bikas Das, Zhongming Zhao
Summary: In this study, a deep learning framework based on a convolutional neural network was developed for the accurate identification of GBM subtypes. The deep learning model outperformed traditional machine learning algorithms in subtype identification. The study also identified genotype-phenotype relationships of GBM subtypes and subtype-specific predictive biomarkers, providing potential diagnostic and treatment options.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Erola Pairo-Castineira, Konrad Rawlik, Andrew D. Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A. McConkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D. Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G. Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny McAuley, Hugh Montgomery, Peter J. M. Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, Jose A. Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Jian Yang, Chris P. Ponting, James F. Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D. Luchessi, Esteban J. Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C. Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J. Kenneth Baillie
Summary: This study analyzed genetic data from 24,202 severe COVID-19 cases and identified potentially druggable targets, including inflammatory signaling, monocyte-macrophage activation and endothelial permeability, immunometabolism, and host factors required for viral entry and replication.
Article
Biochemistry & Molecular Biology
Mingming Lu, Yadong Zhang, Fengchun Yang, Jialin Mai, Qianwen Gao, Xiaowei Xu, Hongyu Kang, Li Hou, Yunfei Shang, Qiheng Qain, Jie Liu, Meiye Jiang, Hao Zhang, Congfan Bu, Jinyue Wang, Zhewen Zhang, Zaichao Zhang, Jingyao Zeng, Jiao Li, Jingfa Xiao
Summary: Transcriptome-wide association studies have led to a better understanding of genetic variants in regulating diseases and traits. However, there is a lack of databases curating public TWAS information. To fill this gap, TWAS Atlas is introduced as an integrated knowledgebase with 401,266 gene-trait associations from 200 publications, providing a user-friendly web interface for browsing, searching, and downloading relevant information.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Heather J. Zhou, Lei Li, Yumei Li, Wei Li, Jingyi Jessica Li
Summary: This study benchmarks popular hidden variable inference methods and finds that principal component analysis (PCA) not only underlies the statistical methodology behind these methods, but is also faster, better-performing, and easier to interpret and use. To help researchers use PCA in their QTL analysis, the authors provide an R package and a detailed guide, believing that using PCA will substantially improve and simplify hidden variable inference in QTL mapping, as well as increase the transparency and reproducibility of QTL research.
Article
Multidisciplinary Sciences
Michael M. Safaee, Elaina J. Wang, Saket Jain, Jia-Shu Chen, Sabraj Gill, Allison C. Zheng, Joseph H. Garcia, Angad S. Beniwal, Y. Tran, Alan T. Nguyen, Melissa Trieu, Kevin Leung, Jim Wells, James M. Maclean, Keith Wycoff, Manish K. Aghi
Summary: This study demonstrates the heterogeneous expression of CD97 in human GBM and its association with the MAPK/Erk and PI3K/Akt pathways. CD97 knockout decreases Akt activation, but targeting CD97 does not affect MAPK/Erk activation or slow GBM cell proliferation. It also increases levels of glycolytic and oxidative phosphorylation metabolites. Tumors with high CD97 expression are associated with changes in the immune microenvironment. Overall, CD97 has conflicting effects on tumor cell proliferation and metabolic pathways, but exerts pro-tumoral effects on the tumor immune microenvironment.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Emine Guven, Muhammad Afzal, Imran Kazmi
Summary: This study identified core genes strongly associated with the progression of GBM through gene expression datasets and various analysis methods. These genes may serve as potential markers for the prognosis and diagnosis of GBM.
Review
Biochemistry & Molecular Biology
Marianna Makowska, Beata Smolarz, Hanna Romanowicz
Summary: Glioblastoma multiforme (GBM) is a common, malignant brain tumor with a poor prognosis. Traditional treatments have limited success due to the tumor's infiltrating growth and resistance. The search for new therapies is crucial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Fatemeh Tirgar, Zahra Azizi, Saereh Hosseindoost, Mahmoudreza Hadjighassem
Summary: This study demonstrates that olfactory ensheathing cells (OECs) can be used as a novel carrier for gene therapy in glioblastoma multiforme (GBM) animal models. OECs have high migration capability and can effectively suppress tumor progression.
Article
Biochemical Research Methods
Jiajun Yang, Dongyang Wang, Yanbo Yang, Wenqian Yang, Weiwei Jin, Xiaohui Niu, Jing Gong
Summary: This study comprehensively evaluated the impact of eight commonly used normalization methods on eQTL identification using RNA-seq and genotype data from different cancer samples. Our results showed that different methods could cause 20-30% differences in the final results, with TMM identified as the optimal normalization method.
The combination of methods was found to not only identify more cis-eQTLs, but also improve the performance of the ROC curve, suggesting the potential benefits of considering pairwise combinations of normalization methods in eQTL analysis.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Chemistry, Multidisciplinary
P. Soma Yasaswi, Karishma Shetty, Khushwant S. Yadav
Summary: GBM, a life-threatening IV grade glioma brain cancer, remains a challenge to treat due to the toxic nature and fast degradation of TMZ, along with lack of targeting ability increasing chances of systemic toxicities. Nano-enabled technology improves the efficiency of TMZ and reduces toxicity to healthy tissues.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Agriculture, Dairy & Animal Science
Mackenzie A. Marrella, Fernando H. Biase
Summary: This study suggests that it is not necessary to transform RNA-sequencing data to fit a normal distribution prior to eQTL analysis, and the differential gene expression framework can be used instead. This approach can detect biologically relevant variants that might be missed with data transformation.
JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY
(2023)
Review
Immunology
Boyuan Huang, Xuesong Li, Yuntao Li, Jin Zhang, Zhitao Zong, Hongbo Zhang
Summary: Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor in the central nervous system. Immunotherapy has shown promising results in the treatment of GBM, but future developments will require an integrated approach with various treatment modalities and specific targeted therapies for the tumor microenvironment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Aysenur Yazici, Lisa Marinelli, Ivana Cacciatore, Bugrahan Emsen, Piera Eusepi, Giuseppe Di Biase, Antonio Di Stefano, Adil Mardinoglu, Hasan Turkez
Summary: This study investigated the in vitro effect of CVC codrugs on human glioblastoma cell line for the first time. The results showed that CVC1-8 codrugs induced cytotoxicity and positive alterations in molecular responses on U87MG cells, with CVC3 and CVC8 modulating important pathways involved in the onset and progression of GBM. These findings suggest that CVC3 and CVC8 could be potential candidates for further investigation in the development of new strategies for preventing and treating GBM.
CURRENT DRUG DELIVERY
(2021)
Article
Cardiac & Cardiovascular Systems
Seung Hoan Choi, Sean J. Jurgens, Lu-Chen Weng, James P. Pirruccello, Carolina Roselli, Mark Chaffin, Christina J. -Y. Lee, Amelia W. Hall, Amit V. Khera, Kathryn L. Lunetta, Steven A. Lubitz, Patrick T. Ellinor
CIRCULATION RESEARCH
(2020)
Article
Cardiac & Cardiovascular Systems
Nathan R. Tucker, Mark Chaffin, Stephen J. Fleming, Amelia W. Hall, Victoria A. Parsons, Kenneth C. Bedi, Amer-Denis Akkad, Caroline N. Herndon, Alessandro Arduini, Irinna Papangeli, Carolina Roselli, Francois Aguet, Seung Hoan Choi, Kristin G. Ardlie, Mehrtash Babadi, Kenneth B. Margulies, Christian M. Stegmann, Patrick T. Ellinor
Article
Multidisciplinary Sciences
Ioanna Ntalla, Lu-Chen Weng, James H. Cartwright, Amelia Weber Hall, Gardar Sveinbjornsson, Nathan R. Tucker, Seung Hoan Choi, Mark D. Chaffin, Carolina Roselli, Michael R. Barnes, Borbala Mifsud, Helen R. Warren, Caroline Hayward, Jonathan Marten, James J. Cranley, Maria Pina Concas, Paolo Gasparini, Thibaud Boutin, Ivana Kolcic, Ozren Polasek, Igor Rudan, Nathalia M. Araujo, Maria Fernanda Lima-Costa, Antonio Luiz P. Ribeiro, Renan P. Souza, Eduardo Tarazona-Santos, Vilmantas Giedraitis, Erik Ingelsson, Anubha Mahajan, Andrew P. Morris, Fabiola M. Del Greco, Luisa Foco, Martin Gogele, Andrew A. Hicks, James P. Cook, Lars Lind, Cecilia M. Lindgren, Johan Sundstrom, Christopher P. Nelson, Muhammad B. Riaz, Nilesh J. Samani, Gianfranco Sinagra, Sheila Ulivi, Mika Kahonen, Pashupati P. Mishra, Nina Mononen, Kjell Nikus, Mark J. Caulfield, Anna Dominiczak, Sandosh Padmanabhan, May E. Montasser, Jeff R. O'Connell, Kathleen Ryan, Alan R. Shuldiner, Stefanie Aeschbacher, David Conen, Lorenz Risch, Sebastien Theriault, Nina Hutri-Kahonen, Terho Lehtimaki, Leo-Pekka Lyytikainen, Olli T. Raitakari, Catriona L. K. Barnes, Harry Campbell, Peter K. Joshi, James F. Wilson, Aaron Isaacs, Jan A. Kors, Cornelia M. van Duijn, Paul L. Huang, Vilmundur Gudnason, Tamara B. Harris, Lenore J. Launer, Albert Smith, Erwin P. Bottinger, Ruth J. F. Loos, Girish N. Nadkarni, Michael H. Preuss, Adolfo Correa, Hao Mei, James Wilson, Thomas Meitinger, Martina Mueller-Nurasyid, Annette Peters, Melanie Waldenberger, Massimo Mangino, Timothy D. Spector, Michiel Rienstra, Yordi J. van de Vegte, Pim van der Harst, Niek Verweij, Stefan Kaab, Katharina Schramm, Moritz F. Sinner, Konstantin Strauch, Michael J. Cutler, Diane Fatkin, Barry London, Morten Olesen, Dan M. Roden, M. Benjamin Shoemaker, J. Gustav Smith, Mary L. Biggs, Joshua C. Bis, Jennifer A. Brody, Bruce M. Psaty, Kenneth Rice, Nona Sotoodehnia, Alessandro De Grandi, Christian Fuchsberger, Cristian Pattaro, Peter P. Pramstaller, Ian Ford, J. Wouter Jukema, Peter W. Macfarlane, Stella Trompet, Marcus Doerr, Stephan B. Felix, Uwe Voelker, Stefan Weiss, Aki S. Havulinna, Antti Jula, Katri Saaksjarvi, Veikko Salomaa, Xiuqing Guo, Susan R. Heckbert, Henry J. Lin, Jerome Rotter, Kent D. Taylor, Jie Yao, Renee de Mutsert, Arie C. Maan, Dennis O. Mook-Kanamori, Raymond Noordam, Francesco Cucca, Jun Ding, Edward G. Lakatta, Yong Qian, Kirill Tarasov, Daniel Levy, Honghuang Lin, Christopher H. Newton-Cheh, Kathryn L. Lunetta, Alison D. Murray, David J. Porteous, Blair H. Smith, Bruno H. Stricker, Andre Uitterlinden, Marten E. van den Berg, Jeffrey Haessler, Rebecca D. Jackson, Charles Kooperberg, Ulrike Peters, Alexander P. Reiner, Eric A. Whitsel, Alvaro Alonso, Dan E. Arking, Eric Boerwinkle, Georg B. Ehret, Elsayed Z. Soliman, Christy L. Avery, Stephanie M. Gogarten, Kathleen F. Kerr, Cathy C. Laurie, Amanda A. Seyerle, Adrienne Stilp, Solmaz Assa, M. Abdullah Said, M. Yldau van der Ende, Pier D. Lambiase, Michele Orini, Julia Ramirez, Stefan Van Duijvenboden, David O. Arnar, Daniel F. Gudbjartsson, Hilma Holm, Patrick Sulem, Gudmar Thorleifsson, Rosa B. Thorolfsdottir, Unnur Thorsteinsdottir, Emelia J. Benjamin, Andrew Tinker, Kari Stefansson, Patrick T. Ellinor, Yalda Jamshidi, Steven A. Lubitz, Patricia B. Munroe
NATURE COMMUNICATIONS
(2020)
Article
Cardiac & Cardiovascular Systems
Antoinette F. van Ouwerkerk, Amelia W. Hall, Zachary A. Kadow, Sonja Lazarevic, Jasmeet S. Reyat, Nathan R. Tucker, Rangarajan D. Nadadur, Fernanda M. Bosada, Valerio Bianchi, Patrick T. Ellinor, Larissa Fabritz, James F. Martin, Wouter de Laat, Paulus Kirchhof, Ivan P. Moskowitz, Vincent M. Christoffels
CIRCULATION RESEARCH
(2020)
Article
Cardiac & Cardiovascular Systems
Lu-Chen Weng, Amelia Weber Hall, Seung Hoan Choi, Sean J. Jurgens, Jeffrey Haessler, Nathan A. Bihlmeyer, Niels Grarup, Honghuang Lin, Alexander Teumer, Ruifang Li-Gao, Jie Yao, Xiuqing Guo, Jennifer A. Brody, Martina Mueller-Nurasyid, Katharina Schramm, Niek Verweij, Marten E. van den Berg, Jessica van Setten, Aaron Isaacs, Julia Ramirez, Helen R. Warren, Sandosh Padmanabhan, Jan A. Kors, Rudolf A. de Boer, Peter van der Meer, Moritz F. Sinner, Melanie Waldenberger, Bruce M. Psaty, Kent D. Taylor, Uwe Voelker, Jorgen K. Kanters, Man Li, Alvaro Alonso, Marco V. Perez, Ilonca Vaartjes, Michiel L. Bots, Paul L. Huang, Susan R. Heckbert, Henry J. Lin, Jelena Kornej, Patricia B. Munroe, Cornelia M. van Duijn, Folkert W. Asselbergs, Bruno H. Stricker, Pim van der Harst, Stefan Kaeaeb, Annette Peters, Nona Sotoodehnia, Jerome I. Rotter, Dennis O. Mook-Kanamori, Marcus Doerr, Stephan B. Felix, Allan Linneberg, Torben Hansen, Dan E. Arking, Charles Kooperberg, Emelia J. Benjamin, Kathryn L. Lunetta, Patrick T. Ellinor, Steven A. Lubitz
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2020)
Article
Cardiac & Cardiovascular Systems
Amelia Weber Hall, Mark Chaffin, Carolina Roselli, Honghuang Lin, Steven A. Lubitz, Valerio Bianchi, Geert Geeven, Kenneth Bedi, Kenneth B. Margulies, Wouter de Laat, Nathan R. Tucker, Patrick T. Ellinor
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2020)
Article
Cardiac & Cardiovascular Systems
Seung Hoan Choi, Sean J. Jurgens, Christopher M. Haggerty, Amelia W. Hall, Jennifer L. Halford, Valerie N. Morrill, Lu-Chen Weng, Braxton Lagerman, Tooraj Mirshahi, Mary Pettinger, Xiuqing Guo, Henry J. Lin, Alvaro Alonso, Elsayed Z. Soliman, Jelena Kornej, Honghuang Lin, Arden Moscati, Girish N. Nadkarni, Jennifer A. Brody, Kerri L. Wiggins, Brian E. Cade, Jiwon Lee, Christina Austin-Tse, Tom Blackwell, Mark D. Chaffin, Christina J-Y Lee, Heidi L. Rehm, Carolina Roselli, Susan Redline, Braxton D. Mitchell, Nona Sotoodehnia, Bruce M. Psaty, Susan R. Heckbert, Ruth J. F. Loos, Ramachandran S. Vasan, Emelia J. Benjamin, Adolfo Correa, Eric Boerwinkle, Dan E. Arking, Jerome Rotter, Stephen S. Rich, Eric A. Whitsel, Marco Perez, Charles Kooperberg, Brandon K. Fornwalt, Kathryn L. Lunetta, Patrick T. Ellinor, Steven A. Lubitz
Summary: This study identified rare coding variants associated with population-based electrocardiographic intervals, uncovering known monogenic SCD genes and novel genes involved in cardiac conduction. These harmful variants showed incomplete penetrance but significantly increased the risk of abnormal electrocardiographic intervals.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2021)
Article
Genetics & Heredity
James P. Pirruccello, Mark D. Chaffin, Elizabeth L. Chou, Stephen J. Fleming, Honghuang Lin, Mahan Nekoui, Shaan Khurshid, Samuel F. Friedman, Alexander G. Bick, Alessandro Arduini, Lu-Chen Weng, Seung Hoan Choi, Amer-Denis Akkad, Puneet Batra, Nathan R. Tucker, Amelia W. Hall, Carolina Roselli, Emelia J. Benjamin, Shamsudheen K. Vellarikkal, Rajat M. Gupta, Christian M. Stegmann, Dejan Juric, James R. Stone, Ramachandran S. Vasan, Jennifer E. Ho, Udo Hoffmann, Steven A. Lubitz, Anthony A. Philippakis, Mark E. Lindsay, Patrick T. Ellinor
Summary: Genome-wide association analyses identified variants associated with thoracic aortic diameter and polygenic score for ascending aortic diameter was correlated with a diagnosis of thoracic aortic aneurysm. Enlargement or aneurysm of the aorta predisposes to dissection, and a deep learning model along with genome-wide association studies successfully identified loci associated with ascending and descending thoracic aortic diameter, highlighting the potential for rapidly defining quantitative traits with deep learning in biomedical images.
Article
Genetics & Heredity
Sean J. Jurgens, Seung Hoan Choi, Valerie N. Morrill, Mark Chaffin, James P. Pirruccello, Jennifer L. Halford, Lu-Chen Weng, Victor Nauffal, Carolina Roselli, Amelia W. Hall, Matthew T. Oetjens, Braxton Lagerman, David P. VanMaanen, Regeneron Genetics Center, Krishna G. Aragam, Kathryn L. Lunetta, Christopher M. Haggerty, Steven A. Lubitz, Patrick T. Ellinor
Summary: This study analyzed the contribution of rare variants to cardiometabolic diseases using data from UK Biobank. They identified gene-based associations and found several genes associated with height, blood lipid, or glucose levels.
Article
Cardiac & Cardiovascular Systems
Victor Nauffal, Valerie N. Morrill, Sean J. Jurgens, Seung Hoan Choi, Amelia W. Hall, Lu-Chen Weng, Jennifer L. Halford, Christina Austin-Tse, Christopher M. Haggerty, Stephanie L. Harris, Eugene K. Wong, Alvaro Alonso, Dan E. Arking, Emelia J. Benjamin, Eric Boerwinkle, Yuan- Min, Adolfo Correa, Brandon K. Fornwalt, Susan R. Heckbert, Charles Kooperberg, Henry J. Lin, Ruth J.f. Loos, Kenneth M. Rice, Namrata Gupta, Thomas W. Blackwell, Braxton D. Mitchell, Alanna C. Morrison, Bruce M. Psaty, Wendy S. Post, Susan Redline, Heidi L. Rehm, Stephen S. Rich, Jerome I. Rotter, Elsayed Z. Soliman, Nona Sotoodehnia, Kathryn L. Lunetta, Patrick T. Ellinor, Steven A. Lubitz
Summary: Using data from large-scale biorepositories, this study found 54 independent loci associated with cardiac repolarization, including 21 novel loci. The findings suggest that both rare variants in genes underlying cardiac repolarization and polygenic risk play a role in determining the duration of QT interval in the population.
Article
Cardiac & Cardiovascular Systems
Sian O'Brien, Andrew P. P. Holmes, Daniel M. M. Johnson, Christopher O'Shea, Molly O'Reilly, Adelisa Avezzu, Jasmeet S. S. Reyat, Amelia W. W. Hall, Clara Apicella, Patrick T. T. Ellinor, Steven Niederer, Nathan R. R. Tucker, Larissa Fabritz, Paulus Kirchhof, Davor Pavlovic, S. Nashitha Kabir
Summary: Atrial fibrillation is a major cause of stroke and heart failure in the elderly, and sodium channel blockers appear to have a relatively low risk of ventricular pro-arrhythmia in patients with this condition. The study found intrinsic differences between atrial and ventricular sodium currents, which may explain the reduced risk in atrial cells.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jennifer L. Halford, Valerie N. Morrill, Seung Hoan Choi, Sean J. Jurgens, Giorgio Melloni, Nicholas A. Marston, Lu-Chen Weng, Victor Nauffal, Amelia W. Hall, Sophia Gunn, Christina A. Austin-Tse, James P. Pirruccello, Shaan Khurshid, Heidi L. Rehm, Emelia J. Benjamin, Eric Boerwinkle, Jennifer A. Brody, Adolfo Correa, Brandon K. Fornwalt, Namrata Gupta, Christopher M. Haggerty, Stephanie Harris, Susan R. Heckbert, Charles C. Hong, Charles Kooperberg, Henry J. Lin, Ruth J. F. Loos, Braxton D. Mitchell, Alanna C. Morrison, Wendy Post, Bruce M. Psaty, Susan Redline, Kenneth M. Rice, Stephen S. Rich, Jerome Rotter, Peter F. Schnatz, Elsayed Z. Soliman, Nona Sotoodehnia, Eugene K. Wong, Marc S. Sabatine, Christian T. Ruff, Kathryn L. Lunetta, Patrick T. Ellinor, Steven A. Lubitz
Summary: Accurate and efficient classification of variant pathogenicity is crucial for research and clinical care. This study demonstrates that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide evidence for variant pathogenicity.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Shaan Khurshid, Julieta Lazarte, James P. Pirruccello, Lu-Chen Weng, Seung Hoan Choi, Amelia W. Hall, Xin Wang, Samuel F. Friedman, Victor Nauffal, Kiran J. Biddinger, Krishna G. Aragam, Puneet Batra, Jennifer E. Ho, Anthony A. Philippakis, Patrick T. Ellinor, Steven A. Lubitz
Summary: A genome-wide association study on 43,000 UK Biobank participants using cardiac magnetic resonance-derived left ventricular mass index identified 12 associations, including 11 novel ones, related to cardiac contractility and cardiomyopathy. The study demonstrates the association between indexed left ventricular mass and incident cardiomyopathy, as well as implantable cardioverter-defibrillator implant. The findings highlight the importance of cardiac magnetic resonance in assessing cardiovascular risk.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Bridget Simonson, Mark Chaffin, Matthew C. Hill, Ondine Atwa, Yasmine Guedira, Harshit Bhasin, Amelia W. Hall, Sikander Hayat, Simon Baumgart, Kenneth C. Bedi, Kenneth B. Margulies, Carla A. Klattenhoff, Patrick T. Ellinor
Summary: Using single-nucleus RNA sequencing and computational analysis, the cellular and molecular signature of ischemic cardiomyopathy (ICM) was investigated. The study revealed alterations in the cellular composition of the ischemic heart, with decreased cardiomyocytes and increased proportions of lymphatic, angiogenic, and arterial endothelial cells in ICM patients. Furthermore, increased LAMININ signaling from endothelial cells and similarities in transcriptional changes were observed between ICM, hypertrophic, and dilated cardiomyopathies, which may help identify potential drug targets for end-stage heart failure.
Article
Cardiac & Cardiovascular Systems
Heather S. Jameson, Alan Hanley, Matthew C. Hill, Ling Xiao, Jiangchuan Ye, Aneesh Bapat, Elsa Ronzier, Amelia Weber Hall, William J. Hucker, Sebastian Clauss, Miranda Barazza, Elizabeth Silber, Julie A. Mina, Nathan R. Tucker, Robert W. Mills, Jin-Tang Dong, David J. Milan, Patrick T. Ellinor
Summary: This study identified the causative genetic variation related to atrial fibrillation (AF) at the ZFHX3 locus and explored the impact of Zfhx3 loss on cardiac function in mice. The results showed that ZFHX3 is the causative gene for AF at the 16q22 locus and its loss leads to cardiac abnormalities and dysregulation of atrial-specific pathways involved in AF susceptibility.
CIRCULATION RESEARCH
(2023)
