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2. Single-Nuclear RNA Sequencing of Endomyocardial Biopsies Identifies Persistence of Donor-Recipient Chimerism With Distinct Signatures in Severe Cardiac Allograft Vasculopathy

Author

Amancherla, Kaushik, Qin, Juan, Hulke, Michelle L, Pfeiffer, Ryan D, Agrawal, Vineet, Sheng, Quanhu, Xu, Yaomin, Schlendorf, Kelly H, Lindenfeld, JoAnn, Shah, Ravi V, Freedman, Jane E, Tucker, Nathan R, and Moslehi, Javid

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Humans, Chimerism, Heart Failure, Heart Transplantation, Biopsy, Allografts, Sequence Analysis, RNA, Graft Rejection, allografts, biopsy, fibroblasts, genomics, myocardium, Biochemistry and Cell Biology, Cardiorespiratory Medicine and Haematology, Medical Physiology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Medical physiology
Published
2023

3. A Beary Good Genome: Haplotype-Resolved, Chromosome-Level Assembly of the Brown Bear (Ursus arctos)

Author

Armstrong, Ellie E, Perry, Blair W, Huang, Yongqing, Garimella, Kiran V, Jansen, Heiko T, Robbins, Charles T, Tucker, Nathan R, and Kelley, Joanna L

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Animals, Chromosomes, Genome, Haplotypes, Humans, Phylogeny, Ursidae, long-read sequencing, comparative genomics, hibernation, Biochemistry and Cell Biology, Evolutionary Biology, Developmental Biology, Biochemistry and cell biology, Evolutionary biology
Abstract

The brown bear (Ursus arctos) is the second largest and most widespread extant terrestrial carnivore on Earth and has recently emerged as a medical model for human metabolic diseases. Here, we report a fully phased chromosome-level assembly of a male North American brown bear built by combining Pacific Biosciences (PacBio) HiFi data and publicly available Hi-C data. The final genome size is 2.47 Gigabases (Gb) with a scaffold and contig N50 length of 70.08 and 43.94 Megabases (Mb), respectively. Benchmarking Universal Single-Copy Ortholog (BUSCO) analysis revealed that 94.5% of single copy orthologs from Mammalia were present in the genome (the highest of any ursid genome to date). Repetitive elements accounted for 44.48% of the genome and a total of 20,480 protein coding genes were identified. Based on whole genome alignment to the polar bear, the brown bear is highly syntenic with the polar bear, and our phylogenetic analysis of 7,246 single-copy orthologs supports the currently proposed species tree for Ursidae. This highly contiguous genome assembly will support future research on both the evolutionary history of the bear family and the physiological mechanisms behind hibernation, the latter of which has broad medical implications.

Published
2022

5. SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart

Author

Valkov, Nedyalka, Das, Avash, Tucker, Nathan R, Li, Guoping, Salvador, Ane M, Chaffin, Mark D, De Oliveira, Getulio Pereira, Kur, Ivan, Gokulnath, Priyanka, Ziegler, Olivia, Yeri, Ashish, Lu, Shulin, Khamesra, Aushee, Xiao, Chunyang, Rodosthenous, Rodosthenis, Srinivasan, Srimeenakshi, Toxavidis, Vasilis, Tigges, John, Laurent, Louise C, Momma, Stefan, Kitchen, Robert, Ellinor, Patrick, Ghiran, Ionita, and Das, Saumya

Subjects
Biochemistry and Cell Biology, Medical Physiology, Biomedical and Clinical Sciences, Biological Sciences, Heart Disease, Cardiovascular, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, Animals, Cell Communication, Cell Proliferation, Cells, Cultured, Disease Models, Animal, Erythrocytes, Extracellular Vesicles, Female, Healthy Volunteers, Heart Failure, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myocardial Infarction, Myocardium, Myocytes, Cardiac, RNA, Nuclear, RNA-Seq, Signal Transduction, Single-Cell Analysis, Biological sciences, Biomedical and clinical sciences
Abstract

Extracellular vesicles (EVs) mediate intercellular signaling by transferring their cargo to recipient cells, but the functional consequences of signaling are not fully appreciated. RBC-derived EVs are abundant in circulation and have been implicated in regulating immune responses. Here, we use a transgenic mouse model for fluorescence-based mapping of RBC-EV recipient cells to assess the role of this intercellular signaling mechanism in heart disease. Using fluorescent-based mapping, we detected an increase in RBC-EV-targeted cardiomyocytes in a murine model of ischemic heart failure. Single cell nuclear RNA sequencing of the heart revealed a complex landscape of cardiac cells targeted by RBC-EVs, with enrichment of genes implicated in cell proliferation and stress signaling pathways compared with non-targeted cells. Correspondingly, cardiomyocytes targeted by RBC-EVs more frequently express cellular markers of DNA synthesis, suggesting the functional significance of EV-mediated signaling. In conclusion, our mouse model for mapping of EV-recipient cells reveals a complex cellular network of RBC-EV-mediated intercellular communication in ischemic heart failure and suggests a functional role for this mode of intercellular signaling.

Published
2021

7. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Author

Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R, Mifsud, Borbala, Warren, Helen R, Hayward, Caroline, Marten, Jonathan, Cranley, James J, Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M, Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P, Souza, Renan P, Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P, Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A, Cook, James P, Lind, Lars, Lindgren, Cecilia M, Sundström, Johan, Nelson, Christopher P, Riaz, Muhammad B, Samani, Nilesh J, Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P, Mononen, Nina, Nikus, Kjell, Caulfield, Mark J, Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E, O'Connell, Jeff R, Ryan, Kathleen, Shuldiner, Alan R, Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli T, Barnes, Catriona LK, Campbell, Harry, Joshi, Peter K, Wilson, James F, Isaacs, Aaron, Kors, Jan A, van Duijn, Cornelia M, Huang, Paul L, Gudnason, Vilmundur, Harris, Tamara B, Launer, Lenore J, Smith, Albert V, Bottinger, Erwin P, Loos, Ruth JF, Nadkarni, Girish N, Preuss, Michael H, Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D, Rienstra, Michiel, van de Vegte, Yordi J, van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F, Strauch, Konstantin, Cutler, Michael J, Fatkin, Diane, London, Barry, Olesen, Morten, and Roden, Dan M

Subjects
Humans, Cardiovascular Diseases, Genetic Predisposition to Disease, Electrocardiography, Gene Expression, Multifactorial Inheritance, Quantitative Trait Loci, Female, Male, Arrhythmias, Cardiac, Genetic Variation, Genome-Wide Association Study, Genetic Loci, Endophenotypes, Arrhythmias, Cardiac
Abstract

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

Published
2020

8. Transcriptome variation in human tissues revealed by long-read sequencing

Author

Glinos, Dafni A., Garborcauskas, Garrett, Hoffman, Paul, Ehsan, Nava, Jiang, Lihua, Gokden, Alper, Dai, Xiaoguang, Aguet, François, Brown, Kathleen L., Garimella, Kiran, Bowers, Tera, Costello, Maura, Ardlie, Kristin, Jian, Ruiqi, Tucker, Nathan R., Ellinor, Patrick T., Harrington, Eoghan D., Tang, Hua, Snyder, Michael, Juul, Sissel, Mohammadi, Pejman, MacArthur, Daniel G., Lappalainen, Tuuli, and Cummings, Beryl B.

Published
2022
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9. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy

Author

Chaffin, Mark, Papangeli, Irinna, Simonson, Bridget, Akkad, Amer-Denis, Hill, Matthew C., Arduini, Alessandro, Fleming, Stephen J., Melanson, Michelle, Hayat, Sikander, Kost-Alimova, Maria, Atwa, Ondine, Ye, Jiangchuan, Bedi, Jr, Kenneth C., Nahrendorf, Matthias, Kaushik, Virendar K., Stegmann, Christian M., Margulies, Kenneth B., Tucker, Nathan R., and Ellinor, Patrick T.

Published
2022
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11. Deep learning enables genetic analysis of the human thoracic aorta

Author

Pirruccello, James P., Chaffin, Mark D., Chou, Elizabeth L., Fleming, Stephen J., Lin, Honghuang, Nekoui, Mahan, Khurshid, Shaan, Friedman, Samuel F., Bick, Alexander G., Arduini, Alessandro, Weng, Lu-Chen, Choi, Seung Hoan, Akkad, Amer-Denis, Batra, Puneet, Tucker, Nathan R., Hall, Amelia W., Roselli, Carolina, Benjamin, Emelia J., Vellarikkal, Shamsudheen K., Gupta, Rajat M., Stegmann, Christian M., Juric, Dejan, Stone, James R., Vasan, Ramachandran S., Ho, Jennifer E., Hoffmann, Udo, Lubitz, Steven A., Philippakis, Anthony A., Lindsay, Mark E., and Ellinor, Patrick T.

Published
2022
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12. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Author

Muus, Christoph, Luecken, Malte D., Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit Dhaval, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik A., Duong, Elizabeth Thu, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam L., Chung, Hattie, Montoro, Daniel T., Adams, Taylor, Aliee, Hananeh, Allon, Samuel J., Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh T., Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas M., Cuoco, Michael S., Cuomo, Anna S. E., Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David S., Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin J., Habermann, Arun C., Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros S., Kuo, Christin S., Larsson, Ludvig, Leney-Greene, Michael A., Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif S., Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph H., Mbano, Ian M., McAdams, Alexi M., Nabhan, Ahmad N., Nyquist, Sarah K., Penland, Lolita, Poirion, Olivier B., Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas C., Shea, Conor V., Shi, Xingyi, Sinha, Rahul, Sit, Rene V., Slowikowski, Kamil, Slyper, Michal, Smith, Neal P., Sountoulidis, Alex, Strunz, Maximilian, Sullivan, Travis B., Sun, Dawei, Talavera-López, Carlos, Tan, Peng, Tantivit, Jessica, Travaglini, Kyle J., Tucker, Nathan R., Vernon, Katherine A., Wadsworth, Marc H., Waldman, Julia, Wang, Xiuting, Xu, Ke, Yan, Wenjun, Zhao, William, and Ziegler, Carly G. K.

Published
2021
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14. Transcriptional profile of the rat cardiovascular system at single cell resolution

Author

Arduini, Alessandro, primary, Fleming, Stephen J., additional, Xiao, Ling, additional, Hall, Amelia W., additional, Akkad, Amer-Denis, additional, Chaffin, Mark, additional, Bendinelli, Kayla J., additional, Tucker, Nathan R., additional, Papangeli, Irinna, additional, Mantineo, Helene, additional, Babadi, Mehrtash, additional, Stegmann, Christian M., additional, García-Cardeña, Guillermo, additional, Lindsay, Mark E., additional, Klattenhoff, Carla, additional, and Ellinor, Patrick T., additional

Published
2023
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15. Loss of the Atrial Fibrillation-Related Gene, Zfhx3 , Results in Atrial Dilation and Arrhythmias

Author

Jameson, Heather S., primary, Hanley, Alan, additional, Hill, Matthew C., additional, Xiao, Ling, additional, Ye, Jiangchuan, additional, Bapat, Aneesh, additional, Ronzier, Elsa, additional, Hall, Amelia Weber, additional, Hucker, William J., additional, Clauss, Sebastian, additional, Barazza, Miranda, additional, Silber, Elizabeth, additional, Mina, Julie A., additional, Tucker, Nathan R., additional, Mills, Robert W., additional, Dong, Jin-Tang, additional, Milan, David J., additional, and Ellinor, Patrick T., additional

Published
2023
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16. Transcriptional and Cellular Diversity of the Human Heart

Author

Tucker, Nathan R., Chaffin, Mark, Fleming, Stephen J., Hall, Amelia W., Parsons, Victoria A., Bedi, Kenneth C., Jr, Akkad, Amer-Denis, Herndon, Caroline N., Arduini, Alessandro, Papangeli, Irinna, Roselli, Carolina, Aguet, François, Choi, Seung Hoan, Ardlie, Kristin G., Babadi, Mehrtash, Margulies, Kenneth B., Stegmann, Christian M., and Ellinor, Patrick T.

Published
2020
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18. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

Author

van Ouwerkerk, Antoinette F., Hall, Amelia W., Kadow, Zachary A., Lazarevic, Sonja, Reyat, Jasmeet S., Tucker, Nathan R., Nadadur, Rangarajan D., Bosada, Fernanda M., Bianchi, Valerio, Ellinor, Patrick T., Fabritz, Larissa, Martin, James F., de Laat, Wouter, Kirchhof, Paulus, Moskowitz, Ivan P., and Christoffels, Vincent M.

Published
2020
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19. Multi-ethnic genome-wide association study for atrial fibrillation

Author

Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D., Aragam, Krishna G., Arking, Dan E., Barnard, John, Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Boerwinkle, Eric, Bottinger, Erwin B., Brody, Jennifer A., Calkins, Hugh, Campbell, Archie, Cappola, Thomas P., Carlquist, John, Chasman, Daniel I., Chen, Lin Y., Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E., Chung, Mina K., Cole, John W., Conen, David, Cook, James, Crijns, Harry J., Cutler, Michael J., Damrauer, Scott M., Daniels, Brian R., Darbar, Dawood, Delgado, Graciela, Denny, Joshua C., Dichgans, Martin, Dörr, Marcus, Dudink, Elton A., Dudley, Samuel C., Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B., Ford, Ian, Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Hernesniemi, Jussi, Hocking, Lynne J., Hofman, Albert, Horimoto, Andrea R. V. R., Huang, Jie, Huang, Paul L., Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kamatani, Yoichiro, Kane, John P., Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L., Kirchhof, Paulus, Kleber, Marcus E., Knight, Stacey, Krieger, Jose E., Kubo, Michiaki, Launer, Lenore J., Laurikka, Jari, Lehtimäki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N., Li, Man, Lim, Hong Euy, Lin, Henry J., Lin, Honghuang, Lind, Lars, Lindgren, Cecilia M., Lokki, Marja-Liisa, London, Barry, Loos, Ruth J. F., Low, Siew-Kee, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., März, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Müller-Nurasyid, Martina, Natale, Andrea, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Niemeijer, Maartje N., Nikus, Kjell, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Olesen, Morten S., Orho-Melander, Marju, Padmanabhan, Sandosh, Pak, Hui-Nam, Paré, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribasés, Marta, Ridker, Paul M., Rienstra, Michiel, Risch, Lorenz, Roden, Dan M., Rosand, Jonathan, Rosenberg, Michael A., Rost, Natalia, Rotter, Jerome I., Saba, Samir, Sandhu, Roopinder K., Schnabel, Renate B., Schramm, Katharina, Schunkert, Heribert, Schurman, Claudia, Scott, Stuart A., Seppälä, Ilkka, Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Siland, Joylene E., Sinisalo, Juha, Sinner, Moritz F., Slowik, Agnieszka, Smith, Albert V., Smith, Blair H., Smith, J. Gustav, Smith, Jonathan D., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Stricker, Bruno H., Sun, Albert, Sun, Han, Svendsen, Jesper H., Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Thériault, Sébastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Gelder, Isabelle C., Van Wagoner, David R., Verweij, Niek, Vlachopoulou, Efthymia, Völker, Uwe, Wang, Biqi, Weeke, Peter E., Weijs, Bob, Weiss, Raul, Weiss, Stefan, Wells, Quinn S., Wiggins, Kerri L., Wong, Jorge A., Woo, Daniel, Worrall, Bradford B., Yang, Pil-Sung, Yao, Jie, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A., Lunetta, Kathryn L., and Ellinor, Patrick T.

Published
2018
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21. Deep learning enables genetic analysis of the human thoracic aorta

Author

Pirruccello, James P., Chaffin, Mark D., Chou, Elizabeth L., Fleming, Stephen J., Lin, Honghuang, Nekoui, Mahan, Khurshid, Shaan, Friedman, Samuel F., Bick, Alexander G., Arduini, Alessandro, Weng, Lu-Chen, Choi, Seung Hoan, Akkad, Amer-Denis, Batra, Puneet, Tucker, Nathan R., Hall, Amelia W., Roselli, Carolina, Benjamin, Emelia J., Vellarikkal, Shamsudheen K., Gupta, Rajat M., Stegmann, Christian M., Juric, Dejan, Stone, James R., Vasan, Ramachandran S., Ho, Jennifer E., Hoffmann, Udo, Lubitz, Steven A., Philippakis, Anthony A., Lindsay, Mark E., and Ellinor, Patrick T.

Abstract

Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, identifying 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (hazard ratio = 1.43 per s.d., confidence interval 1.32–1.54, P= 3.3 × 10−20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.

Published
2024
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23. Sex-specific responses to slow progressive pressure overload in a large animal model of HFpEF

Author

Eaton, Deborah M., primary, Berretta, Remus M., additional, Lynch, Jacqueline E., additional, Travers, Joshua G., additional, Pfeiffer, Ryan D., additional, Hulke, Michelle L., additional, Zhao, Huaqing, additional, Hobby, Alexander R. H., additional, Schena, Giana, additional, Johnson, Jaslyn P., additional, Wallner, Markus, additional, Lau, Edward, additional, Lam, Maggie P. Y., additional, Woulfe, Kathleen C., additional, Tucker, Nathan R., additional, McKinsey, Timothy A., additional, Wolfson, Marla R., additional, and Houser, Steven R., additional

Published
2022
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24. COVID-19 and Cardiovascular Disease

Author

Chung, Mina K., Zidar, David A., Bristow, Michael R., Cameron, Scott J., Chan, Timothy, Harding, Clifford V., Kwon, Deborah H., Singh, Tamanna, Tilton, John C., Tsai, Emily J., Tucker, Nathan R., Barnard, John, and Loscalzo, Joseph

Subjects
Gene Expression, Virus Attachment, Review, Renin-Angiotensin System, angiotensin-converting enzyme 2, Risk Factors, magnetic resonance imaging, Humans, Myocytes, Cardiac, RNA, Messenger, thrombosis, Ventricular Remodeling, SARS-CoV-2, Myocardium, COVID-19, Virus Internalization, Platelet Activation, Neuropilin-1, Troponin, Return to Sport, inflammation, Cardiovascular Diseases, Immune System, Spike Glycoprotein, Coronavirus, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiomyopathies, Biomarkers
Abstract

Supplemental Digital Content is available in the text., A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.

Published
2021

25. Single-nuclear RNA sequencing of endomyocardial biopsies identifies persistence of donor-recipient chimerism with distinct signatures in severe cardiac allograft vasculopathy

Author

Amancherla, Kaushik, primary, Qin, Juan, additional, Hulke, Michelle L, additional, Pfeiffer, Ryan D, additional, Agrawal, Vineet, additional, Sheng, Quanhu, additional, Xu, Yaomin, additional, Schlendorf, Kelly H, additional, Lindenfeld, JoAnn, additional, Shah, Ravi V, additional, Freedman, Jane E, additional, Tucker, Nathan R, additional, and Moslehi, Javid, additional

Published
2022
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27. Diminished PRRX1 Expression Is Associated With Increased Risk of Atrial Fibrillation and Shortening of the Cardiac Action Potential

Author

Tucker, Nathan R., Dolmatova, Elena V., Lin, Honghuang, Cooper, Rebecca R., Ye, Jiangchuan, Hucker, William J., Jameson, Heather S., Parsons, Victoria A., Weng, Lu-Chen, Mills, Robert W., Sinner, Moritz F., Imakaev, Maxim, Leyton-Mange, Jordan, Vlahakes, Gus, Benjamin, Emelia J., Lunetta, Kathryn L., Lubitz, Steven A., Mirny, Leonid, Milan, David J., and Ellinor, Patrick T.

Published
2017
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30. Clinico-histopathologic and single-nuclei RNA-sequencing insights into cardiac injury and microthrombi in critical COVID-19

Author

Brener, Michael I., primary, Hulke, Michelle L., additional, Fukuma, Nobuaki, additional, Golob, Stephanie, additional, Zilinyi, Robert S., additional, Zhou, Zhipeng, additional, Tzimas, Christos, additional, Russo, Ilaria, additional, McGroder, Claire, additional, Pfeiffer, Ryan D., additional, Chong, Alexander, additional, Zhang, Geping, additional, Burkhoff, Daniel, additional, Leon, Martin B., additional, Maurer, Mathew S., additional, Moses, Jeffrey W., additional, Uhlemann, Anne-Catrin, additional, Hibshoosh, Hanina, additional, Uriel, Nir, additional, Szabolcs, Matthias J., additional, Redfors, Björn, additional, Marboe, Charles C., additional, Baldwin, Matthew R., additional, Tucker, Nathan R., additional, and Tsai, Emily J., additional

Published
2022
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32. Deep learning enables genetic analysis of the human thoracic aorta

Author

Pirruccello, James P., primary, Chaffin, Mark D., additional, Chou, Elizabeth L., additional, Fleming, Stephen J., additional, Lin, Honghuang, additional, Nekoui, Mahan, additional, Khurshid, Shaan, additional, Friedman, Samuel F., additional, Bick, Alexander G., additional, Arduini, Alessandro, additional, Weng, Lu-Chen, additional, Choi, Seung Hoan, additional, Akkad, Amer-Denis, additional, Batra, Puneet, additional, Tucker, Nathan R., additional, Hall, Amelia W., additional, Roselli, Carolina, additional, Benjamin, Emelia J., additional, Vellarikkal, Shamsudheen K., additional, Gupta, Rajat M., additional, Stegmann, Christian M., additional, Juric, Dejan, additional, Stone, James R., additional, Vasan, Ramachandran S., additional, Ho, Jennifer E., additional, Hoffmann, Udo, additional, Lubitz, Steven A., additional, Philippakis, Anthony A., additional, Lindsay, Mark E., additional, and Ellinor, Patrick T., additional

Published
2021
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33. Abstract 14422: Molecular Pathogenesis of Cardiac Microthrombi in Fatal Covid-19: Insights from Clinico-histopathologic and Single Nuclei RNA Sequencing Analyses

Author

Fukuma, Nobuaki J, primary, Brener, Michael, additional, Hulke, Michelle, additional, Fukuma, Nobuaki, additional, Golob, Stephanie, additional, Zilinyi, Robert, additional, Zhou, Zhipeng, additional, Tzimas, Christos, additional, Russo, Ilaria, additional, McGroder, Claire, additional, Chong, Alexander, additional, Pfeiffer, Ryan, additional, Geping, Zhang, additional, Uhlemann, Anne-Catrin, additional, Moses, Jeffrey, additional, Leon, Martin, additional, Burkhoff, Daniel, additional, Maurer, Mathew, additional, Redfors, Bjorn, additional, Uriel, Nir, additional, Szabolcs, Matthias, additional, Marboe, Charles C, additional, Baldwin, Matthew, additional, and Tucker, Nathan R, additional

Published
2021
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34. Abstract 8955: Cardiopulmonary Phenotyping of Sex-Based Differences in a Feline Model of HFpEF

Author

Eaton, Deborah M, primary, Berretta, Remus M, additional, Lynch, Jacqueline E, additional, Travers, Joshua G, additional, Woulfe, Kathleen C, additional, Pfeiffer, Ryan D, additional, Hulke, Michelle L, additional, Hobby, Alexander R, additional, Schena, Giana, additional, Johnson, Jaslyn P, additional, Wallner, Markus, additional, Tucker, Nathan R, additional, McKinsey, Timothy A, additional, Wolfson, Marla R, additional, and Houser, Steven R, additional

Published
2021
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35. Molecular Pathophysiology of Cardiac Injury and Cardiac Microthrombi in Fatal COVID-19: Insights from Clinico-histopathologic and Single Nuclei RNA Sequencing Analyses

Author

Fukuma, Nobuaki, primary, Hulke, Michelle L., additional, Brener, Michael I., additional, Golob, Stephanie, additional, Zilinyi, Robert, additional, Zhou, Zhipeng, additional, Tzimas, Christos, additional, Russo, Ilaria, additional, McGroder, Claire, additional, Pfeiffer, Ryan, additional, Chong, Alexander, additional, Zhang, Geping, additional, Burkhoff, Daniel, additional, Leon, Martin B., additional, Maurer, Mathew, additional, Moses, Jeffrey W., additional, Uhlemann, Anne-Catrin, additional, Hibshoosh, Hanina, additional, Uriel, Nir, additional, Szabolcs, Matthias J., additional, Redfors, Björn, additional, Marboe, Charles C., additional, Baldwin, Matthew R., additional, Tucker, Nathan R., additional, and Tsai, Emily J., additional

Published
2021
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37. Beary Good Genome: Haplotype-Resolved, Chromosome-Level Assembly of the Brown Bear (Ursus arctos).

Author

Armstrong, Ellie E, Perry, Blair W, Huang, Yongqing, Garimella, Kiran V, Jansen, Heiko T, Robbins, Charles T, Tucker, Nathan R, and Kelley, Joanna L

Subjects
BROWN bear, POLAR bear, GENOME size, PHYSIOLOGY, MEDICAL model, MAMMALS, GENOMES
Abstract

The brown bear (Ursus arctos) is the second largest and most widespread extant terrestrial carnivore on Earth and has recently emerged as a medical model for human metabolic diseases. Here, we report a fully phased chromosome-level assembly of a male North American brown bear built by combining Pacific Biosciences (PacBio) HiFi data and publicly available Hi-C data. The final genome size is 2.47 Gigabases (Gb) with a scaffold and contig N50 length of 70.08 and 43.94 Megabases (Mb), respectively. Benchmarking Universal Single-Copy Ortholog (BUSCO) analysis revealed that 94.5% of single copy orthologs from Mammalia were present in the genome (the highest of any ursid genome to date). Repetitive elements accounted for 44.48% of the genome and a total of 20,480 protein coding genes were identified. Based on whole genome alignment to the polar bear, the brown bear is highly syntenic with the polar bear, and our phylogenetic analysis of 7,246 single-copy orthologs supports the currently proposed species tree for Ursidae. This highly contiguous genome assembly will support future research on both the evolutionary history of the bear family and the physiological mechanisms behind hibernation, the latter of which has broad medical implications. [ABSTRACT FROM AUTHOR]

Published
2022
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38. Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation

Author

Hall, Amelia Weber, Chaffin, Mark, Roselli, Carolina, Lin, Honghuang, Lubitz, Steven A, Bianchi, Valerio, Geeven, Geert, Bedi, Kenneth, Margulies, Kenneth B, de Laat, Wouter, Tucker, Nathan R, Ellinor, Patrick T, Hall, Amelia Weber, Chaffin, Mark, Roselli, Carolina, Lin, Honghuang, Lubitz, Steven A, Bianchi, Valerio, Geeven, Geert, Bedi, Kenneth, Margulies, Kenneth B, de Laat, Wouter, Tucker, Nathan R, and Ellinor, Patrick T

Abstract

BACKGROUND: Atrial fibrillation (AF) often arises from structural abnormalities in the left atria (LA). Annotation of the noncoding genome in human LA is limited, as are effects on gene expression and chromatin architecture. Many AF-associated genetic variants reside in noncoding regions; this knowledge gap impairs efforts to understand the molecular mechanisms of AF and cardiac conduction phenotypes.METHODS: We generated a model of the LA noncoding genome by profiling 7 histone post-translational modifications (active: H3K4me3, H3K4me2, H3K4me1, H3K27ac, H3K36me3; repressive: H3K27me3, H3K9me3), CTCF binding, and gene expression in samples from 5 individuals without structural heart disease or AF. We used MACS2 to identify peak regions (P<0.01), applied a Markov model to classify regulatory elements, and annotated this model with matched gene expression data. We intersected chromatin states with expression quantitative trait locus, DNA methylation, and HiC chromatin interaction data from LA and left ventricle. Finally, we integrated genome-wide association data for AF and electrocardiographic traits to link disease-related variants to genes.RESULTS: Our model identified 21 epigenetic states, encompassing regulatory motifs, such as promoters, enhancers, and repressed regions. Genes were regulated by proximal chromatin states; repressive states were associated with a significant reduction in gene expression (P<2×10-16). Chromatin states were differentially methylated, promoters were less methylated than repressed regions (P<2×10-16). We identified over 15 000 LA-specific enhancers, defined by homeobox family motifs, and annotated several cardiovascular disease susceptibility loci. Intersecting AF and PR genome-wide association studies loci with long-range chromatin conformation data identified a gene interaction network dominated by NKX2-5, TBX3, ZFHX3, and SYNPO2L.CONCLUSIONS: Profiling the noncoding genome provides new insights into

Published
2020

39. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

Author

van Ouwerkerk, Antoinette F, Hall, Amelia W, Kadow, Zachary A, Lazarevic, Sonja, Reyat, Jasmeet S, Tucker, Nathan R, Nadadur, Rangarajan D, Bosada, Fernanda M, Bianchi, Valerio, Ellinor, Patrick T, Fabritz, Larissa, Martin, James F, de Laat, Wouter, Kirchhof, Paulus, Moskowitz, Ivan P, Christoffels, Vincent M, van Ouwerkerk, Antoinette F, Hall, Amelia W, Kadow, Zachary A, Lazarevic, Sonja, Reyat, Jasmeet S, Tucker, Nathan R, Nadadur, Rangarajan D, Bosada, Fernanda M, Bianchi, Valerio, Ellinor, Patrick T, Fabritz, Larissa, Martin, James F, de Laat, Wouter, Kirchhof, Paulus, Moskowitz, Ivan P, and Christoffels, Vincent M

Abstract

Genome-wide association studies have uncovered over a 100 genetic loci associated with atrial fibrillation (AF), the most common arrhythmia. Many of the top AF-associated loci harbor key cardiac transcription factors, including PITX2, TBX5, PRRX1, and ZFHX3. Moreover, the vast majority of the AF-associated variants lie within noncoding regions of the genome where causal variants affect gene expression by altering the activity of transcription factors and the epigenetic state of chromatin. In this review, we discuss a transcriptional regulatory network model for AF defined by effector genes in Genome-wide association studies loci. We describe the current state of the field regarding the identification and function of AF-relevant gene regulatory networks, including variant regulatory elements, dose-sensitive transcription factor functionality, target genes, and epigenetic states. We illustrate how altered transcriptional networks may impact cardiomyocyte function and ionic currents that impact AF risk. Last, we identify the need for improved tools to identify and functionally test transcriptional components to define the links between genetic variation, epigenetic gene regulation, and atrial function.

Published
2020

40. Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation

Author

CMM Groep Burgering, Genetica, Cancer, Hubrecht Institute with UMC, Hall, Amelia Weber, Chaffin, Mark, Roselli, Carolina, Lin, Honghuang, Lubitz, Steven A, Bianchi, Valerio, Geeven, Geert, Bedi, Kenneth, Margulies, Kenneth B, de Laat, Wouter, Tucker, Nathan R, Ellinor, Patrick T, CMM Groep Burgering, Genetica, Cancer, Hubrecht Institute with UMC, Hall, Amelia Weber, Chaffin, Mark, Roselli, Carolina, Lin, Honghuang, Lubitz, Steven A, Bianchi, Valerio, Geeven, Geert, Bedi, Kenneth, Margulies, Kenneth B, de Laat, Wouter, Tucker, Nathan R, and Ellinor, Patrick T

Published
2020

41. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation

Author

Genetica, Cancer, Hubrecht Institute with UMC, van Ouwerkerk, Antoinette F, Hall, Amelia W, Kadow, Zachary A, Lazarevic, Sonja, Reyat, Jasmeet S, Tucker, Nathan R, Nadadur, Rangarajan D, Bosada, Fernanda M, Bianchi, Valerio, Ellinor, Patrick T, Fabritz, Larissa, Martin, James F, de Laat, Wouter, Kirchhof, Paulus, Moskowitz, Ivan P, Christoffels, Vincent M, Genetica, Cancer, Hubrecht Institute with UMC, van Ouwerkerk, Antoinette F, Hall, Amelia W, Kadow, Zachary A, Lazarevic, Sonja, Reyat, Jasmeet S, Tucker, Nathan R, Nadadur, Rangarajan D, Bosada, Fernanda M, Bianchi, Valerio, Ellinor, Patrick T, Fabritz, Larissa, Martin, James F, de Laat, Wouter, Kirchhof, Paulus, Moskowitz, Ivan P, and Christoffels, Vincent M

Published
2020

42. Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation

Author

Hall, Amelia Weber, primary, Chaffin, Mark, additional, Roselli, Carolina, additional, Lin, Honghuang, additional, Lubitz, Steven A., additional, Bianchi, Valerio, additional, Geeven, Geert, additional, Bedi, Kenneth, additional, Margulies, Kenneth B., additional, de Laat, Wouter, additional, Tucker, Nathan R., additional, and Ellinor, Patrick T., additional

Published
2020
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43. Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 Mediated Myocarditis

Author

Tucker, Nathan R., primary, Chaffin, Mark, additional, Bedi Jr, Kenneth C., additional, Papangeli, Irinna, additional, Akkad, Amer-Denis, additional, Arduini, Alessandro, additional, Hayat, Sikander, additional, Eraslan, Gökcen, additional, Muus, Christoph, additional, Bhattacharyya, Roby P., additional, Stegmann, Christian M., additional, Margulies, Kenneth B., additional, and Ellinor, Patrick T., additional

Published
2020
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44. Deep learning enables genetic analysis of the human thoracic aorta

Author

Pirruccello, James P., primary, Chaffin, Mark D., additional, Fleming, Stephen J., additional, Arduini, Alessandro, additional, Lin, Honghuang, additional, Khurshid, Shaan, additional, Chou, Elizabeth L., additional, Friedman, Samuel N., additional, Bick, Alexander G., additional, Weng, Lu-Chen, additional, Choi, Seung Hoan, additional, Akkad, Amer-Denis, additional, Batra, Puneet, additional, Tucker, Nathan R., additional, Hall, Amelia W., additional, Roselli, Carolina, additional, Benjamin, Emelia J., additional, Vellarikkal, Shamsudheen K., additional, Gupta, Rajat M., additional, Stegman, Christian M., additional, Ho, Jennifer E., additional, Hoffmann, Udo, additional, Lubitz, Steven A., additional, Philippakis, Anthony, additional, Lindsay, Mark E., additional, and Ellinor, Patrick T., additional

Published
2020
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45. Transcriptional and Cellular Diversity of the Human Heart

Author

Tucker, Nathan R., primary, Chaffin, Mark, additional, Fleming, Stephen J., additional, Hall, Amelia W., additional, Parsons, Victoria A., additional, Bedi, Kenneth, additional, Akkad, Amer-Denis, additional, Herndon, Caroline N., additional, Arduini, Alessandro, additional, Papangeli, Irinna, additional, Roselli, Carolina, additional, Aguet, François, additional, Choi, Seung Hoan, additional, Ardlie, Kristin G., additional, Babadi, Mehrtash, additional, Margulies, Kenneth B., additional, Stegmann, Christian M., additional, and Ellinor, Patrick T., additional

Published
2020
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47. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Author

Pulit, Sara L., Weng, Lu-Chen, McArdle, Patrick F, Trinquart, Ludovic, Choi, Seung Hoan, Mitchell, Braxton D., Rosand, Jonathan, de Bakker, Paul I W, Benjamin, Emelia J, Ellinor, Patrick T, Kittner, Steven J, Lubitz, Steven A, Anderson, Christopher D, Christophersen, Ingrid E., Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E., Smith, Albert V., Albert, Christine M., Chaffin, Mark, Tucker, Nathan R., Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A, Low, Siew-Kee, Weeke, Peter E., Müller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Dörr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Thériault, Sébastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati, Siland, Joylene E., Kubo, Michiaki, Smith, Jonathan D., Van Wagoner, David R., Bis, Joshua C., Perz, Siegfried, Psaty, Bruce M., Ridker, Paul M., Magnani, Jared W., Harris, Tamara B., Launer, Lenore J., Shoemaker, M. Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M., Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E., Kähönen, Mika, Risch, Lorenz, Mansur, Alfredo J., Peters, Annette, Smith, Blair H., Lind, Lars, Scott, Stuart A., Lu, Yingchang, Bottinger, Erwin B., Hernesniemi, Jussi, Lindgren, Cecilia M., Wong, Jorge A, Huang, Jie, Eskola, Markku, Morris, Andrew P., Ford, Ian, Reiner, Alex P., Delgado, Graciela, Chen, Lin Y., Chen, Yii-Der Ida, Sandhu, Roopinder K., Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Orho-Melander, arju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Völker, Uwe, Jöckel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Harst, Pim van der, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., März, Winfried, Lehtimäki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Sun, Albert, Anderson, Christopher D., Kääb, Stefan, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Paré, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., Smoller, Sylvia, Sorkin, John, Wang, Xingwu, Selim, Magdy, Pikula, Aleksandra, Wolf, Philip, Seshadri, Sudha, Bakker, Paul de, Chasman, Daniel, Rexrode, Kathryn, Chen, Ida, Rotter, Jerome, Luke, May, Sale, Michelle, Lee, Tsong-Hai, Chang, Ku-Chou, Elkind, Mitchell, Goldstein, Larry, James, Michael Luke, Breteler, Monique, O’Donnell, Chris, Leys, Didier, Carty, Cara, Kidwell, Chelsea, Olesen, Jes, Sharma, Pankaj, Rich, Stephen, Tatlisumak, Turgot, Happola, Olli, Bijlenga, Philippe, Soriano, Carolina, Giralt, Eva, Roquer, Jaume, Jimenez-Conde, Jordi, Cotlarcius, Ioana, Hardy, John, Korostynski, Michal, Boncoraglio, Giorgio, Ballabio, Elena, Parati, Eugenio, Mateusz, Adamski, Urbanik, Andrzej, Dziedzic, Tomasz, Jagiella, Jeremiasz, Gasowski, Jerzy, Wnuk, Marcin, Olszanecki, Rafael, Pera, Joanna, Slowik, Agnieszka, Juchniewicz, Karol Jozef, Levi, Christopher, Nyquist, Paul, Cendes, Iscia, Cabral, Norberto, Franca, Paulo, Goncalves, Anderson, Keller, Lina, Crisby, Milita, Kostulas, Konstantinos, Lemmens, Robin, Ahmadi, Kourosh, Opherk, Christian, Duering, Marco, Gonik, Mariya, Staals, Julie, Burri, Philippe, Sadr-Nabavi, Ariane, Romero, Javier, Biffi, Alessandro, Anderson, Chris, Falcone, Guido, Brouwers, Bart, Du, Rose, Kourkoulis, Christina, Battey, Thomas, Lubitz, Steven, Mueller-Myhsok, Bertram, Meschia, James, Brott, Thomas, Pare, Guillaume, Pichler, Alexander, Enzinger, Christian, Schmidt, Helena, Schmidt, Reinhold, Seiler, Stephan, Blanton, Susan, Yamada, Yoshiji, Bersano, Anna, Rundek, Tatjana, Sacco, Ralph, Chan, Yu-Feng Yvonne, Gschwendtner, Andreas, Deng, Zhen, Barr, Taura, Gwinn, Katrina, Corriveau, Roderick, Singleton, Andrew, Waddy, Salina, Launer, Lenore, Chen, Christopher, Le, Kim En, Lee, Wei Ling, Tan, Eng King, Olugbodi, Akintomi, Rothwell, Peter, Schilling, Sabrina, Mok, Vincent, Lebedeva, Elena, Jern, Christina, Jood, Katarina, Olsson, Sandra, Kim, Helen, Lee, Chaeyoung, Kilarski, Laura, Markus, Hugh, Peycke, Jennifer, Bevan, Steve, Sheu, Wayne, Chiou, Hung Yi, Chern, Joseph, Giraldo, Elias, Taqi, Muhammad, Jain, Vivek, Lam, Olivia, Howard, George, Woo, Daniel, Kittner, Steven, Mitchell, Braxton, Cole, John, O’Connell, Jeff, Milewicz, Dianna, Illoh, Kachikwu, Worrall, Bradford, Stine, Colin, Karaszewski, Bartosz, Werring, David, Sofat, Reecha, Smalley, June, Lindgren, Arne, Hansen, Bjorn, Norrving, Bo, Smith, Gustav, Martin, Juan Jose, Thijs, Vincent, Klijn, Karin, van’t Hof, Femke, Algra, Ale, Macleod, Mary, Perry, Rodney, Arnett, Donna, Pezzini, Alessandro, Padovani, Alessandro, Cramer, Steve, Fisher, Mark, Saleheen, Danish, Broderick, Joseph, Kissela, Brett, Doney, Alex, Cathie, Sudlow, Rannikmae, Kristiina, Silliman, Scott, McDonough, Caitrin, Walters, Matthew, Pedersen, Annie, Nakagawa, Kazuma, Chang, Christy, Dobbins, Mark, McArdle, Patrick, Chang, Yu-Ching, Brown, Robert, Brown, Devin, Holliday, Elizabeth, Kalaria, Raj, Maguire, Jane, John, Attia, Farrall, Martin, Giese, Anne-Katrin, Fornage, Myriam, Majersik, Jennifer, Cushman, Mary, Keene, Keith, Bennett, Siiri, Tirschwell, David, Psaty, Bruce, Reiner, Alex, Longstreth, Will, Spence, David, Montaner, Joan, Fernandez-Cadenas, Israel, Langefeld, Carl, Bushnell, Cheryl, Heitsch, Laura, Lee, Jin-Moo, Sheth, Kevin, Cardiovascular Centre (CVC), Department of Medicine, Clinicum, Transplantation Laboratory, Medicum, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Doctoral Programme in Clinical Research, HUS Neurocenter, Epidemiology, Internal Medicine, Klinische Neurowetenschappen, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)

Subjects
Medizin, 030204 cardiovascular system & hematology, VARIANTS, 3124 Neurology and psychiatry, 0302 clinical medicine, Epidemiology, Genotype, EPIDEMIOLOGY, Stroke, Genetics (clinical), 0303 health sciences, Aspirin, Atrial fibrillation, ASSOCIATION, 3. Good health, LIFETIME RISK, ISCHEMIC-STROKE, Cardiology, Biomarker (medicine), Medical genetics, BURDEN, Medical Genetics, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Clinical Neurology, Single-nucleotide polymorphism, Article, 03 medical and health sciences, Internal medicine, Genetic predisposition, medicine, SNP, cardiovascular diseases, Genotyping, 030304 developmental biology, Genetic association, Medicinsk genetik, Science & Technology, business.industry, 3112 Neurosciences, Heritability, medicine.disease, PREVENTION, ASPIRIN, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery, CAUSATIVE CLASSIFICATION
Abstract

ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10−4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1).ConclusionsGenetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

Published
2018

48. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 210 loci underlying cardiac conduction

Author

Ntalla, Ioanna, primary, Weng, Lu-Chen, additional, Cartwright, James H., additional, Hall, Amelia Weber, additional, Sveinbjornsson, Gardar, additional, Tucker, Nathan R., additional, Choi, Seung Hoan, additional, Chaffin, Mark D., additional, Roselli, Carolina, additional, Barnes, Michael R., additional, Mifsud, Borbala, additional, Warren, Helen R., additional, Hayward, Caroline, additional, Marten, Jonathan, additional, Cranley, James J., additional, Concas, Maria Pina, additional, Gasparini, Paolo, additional, Boutin, Thibaud, additional, Kolcic, Ivana, additional, Polasek, Ozren, additional, Rudan, Igor, additional, Araujo, Nathalia M., additional, Lima-Costa, Maria Fernanda, additional, Ribeiro, Antonio Luiz P., additional, Souza, Renan P., additional, Tarazona-Santos, Eduardo, additional, Giedraitis, Vilmantas, additional, Ingelsson, Erik, additional, Mahajan, Anubha, additional, Morris, Andrew P., additional, Fabiola Del, Greco M., additional, Foco, Luisa, additional, Gögele, Martin, additional, Hicks, Andrew A., additional, Cook, James P., additional, Lind, Lars, additional, Lindgren, Cecilia M., additional, Sundström, Johan, additional, Nelson, Christopher P., additional, Riaz, Muhammad B., additional, Samani, Nilesh J., additional, Sinagra, Gianfranco, additional, Ulivi, Sheila, additional, Kähönen, Mika, additional, Mishra, Pashupati P., additional, Mononen, Nina, additional, Nikus, Kjell, additional, Caulfield, Mark J., additional, Dominiczak, Anna, additional, Padmanabhan, Sandosh, additional, Montasser, May E., additional, O’Connell, Jeff R., additional, Ryan, Kathleen, additional, Shuldiner, Alan R., additional, Aeschbacher, Stefanie, additional, Conen, David, additional, Risch, Lorenz, additional, Thériault, Sébastien, additional, Hutri-Kähönen, Nina, additional, Lehtimäki, Terho, additional, Lyytikäinen, Leo-Pekka, additional, Raitakari, Olli T., additional, Barnes, Catriona L. K., additional, Campbell, Harry, additional, Joshi, Peter K., additional, Wilson, James F., additional, Isaacs, Aaron, additional, Kors, Jan A., additional, van Duijn, Cornelia M., additional, Huang, Paul L., additional, Gudnason, Vilmundur, additional, Harris, Tamara B., additional, Launer, Lenore J., additional, Smith, Albert V., additional, Bottinger, Erwin P., additional, Loos, Ruth J. F., additional, Nadkarni, Girish N., additional, Preuss, Michael H., additional, Correa, Adolfo, additional, Mei, Hao, additional, Wilson, James, additional, Meitinger, Thomas, additional, Müller-Nurasyid, Martina, additional, Peters, Annette, additional, Waldenberger, Melanie, additional, Mangino, Massimo, additional, Spector, Timothy D., additional, Rienstra, Michiel, additional, van de Vegte, Yordi J., additional, van der Harst, Pim, additional, Verweij, Niek, additional, Kääb, Stefan, additional, Schramm, Katharina, additional, Sinner, Moritz F., additional, Strauch, Konstantin, additional, Cutler, Michael J., additional, Fatkin, Diane, additional, London, Barry, additional, Olesen, Morten, additional, Roden, Dan M., additional, Shoemaker, M. Benjamin, additional, Smith, J. Gustav, additional, Biggs, Mary L., additional, Bis, Joshua C., additional, Brody, Jennifer A., additional, Psaty, Bruce M., additional, Rice, Ken, additional, Sotoodehnia, Nona, additional, De Grandi, Alessandro, additional, Fuchsberger, Christian, additional, Pattaro, Cristian, additional, Pramstaller, Peter P., additional, Ford, Ian, additional, Jukema, J. Wouter, additional, Macfarlane, Peter W., additional, Trompet, Stella, additional, Dörr, Marcus, additional, Felix, Stephan B., additional, Völker, Uwe, additional, Weiss, Stefan, additional, Havulinna, Aki S., additional, Jula, Antti, additional, Sääksjärvi, Katri, additional, Salomaa, Veikko, additional, Guo, Xiuqing, additional, Heckbert, Susan R., additional, Lin, Henry J., additional, Rotter, Jerome I., additional, Taylor, Kent D., additional, Yao, Jie, additional, de Mutsert, Renée, additional, Maan, Arie C., additional, Mook-Kanamori, Dennis O., additional, Noordam, Raymond, additional, Cucca, Francesco, additional, Ding, Jun, additional, Lakatta, Edward G., additional, Qian, Yong, additional, Tarasov, Kirill V., additional, Levy, Daniel, additional, Lin, Honghuang, additional, Newton-Cheh, Christopher H., additional, Lunetta, Kathryn L., additional, Murray, Alison D., additional, Porteous, David J., additional, Smith, Blair H., additional, Stricker, Bruno H., additional, Uitterlinden, André, additional, van den Berg, Marten E., additional, Haessler, Jeffrey, additional, Jackson, Rebecca D., additional, Kooperberg, Charles, additional, Peters, Ulrike, additional, Reiner, Alexander P., additional, Whitsel, Eric A., additional, Alonso, Alvaro, additional, Arking, Dan E., additional, Boerwinkle, Eric, additional, Ehret, Georg B., additional, Soliman, Elsayed Z., additional, Avery, Christy L., additional, Gogarten, Stephanie M., additional, Kerr, Kathleen F., additional, Laurie, Cathy C., additional, Seyerle, Amanda A., additional, Stilp, Adrienne, additional, Assa, Solmaz, additional, Said, M. Abdullah, additional, van der Ende, M. Yldau, additional, Lambiase, Pier D., additional, Orini, Michele, additional, Ramirez, Julia, additional, Van Duijvenboden, Stefan, additional, Arnar, David O., additional, Gudbjartsson, Daniel F., additional, Holm, Hilma, additional, Sulem, Patrick, additional, Thorleifsson, Gudmar, additional, Thorolfsdottir, Rosa B., additional, Thorsteinsdottir, Unnur, additional, Benjamin, Emelia J., additional, Tinker, Andrew, additional, Stefansson, Kari, additional, Ellinor, Patrick T., additional, Jamshidi, Yalda, additional, Lubitz, Steven A., additional, and Munroe, Patricia B., additional

Published
2019
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49. Genome-Wide Association Study–Driven Gene-Set Analyses, Genetic, and Functional Follow-Up Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse

Author

Yu, Mengyao, primary, Georges, Adrien, additional, Tucker, Nathan R., additional, Kyryachenko, Sergiy, additional, Toomer, Katelyn, additional, Schott, Jean-Jacques, additional, Delling, Francesca N., additional, Fernandez-Friera, Leticia, additional, Solis, Jorge, additional, Ellinor, Patrick T., additional, Levine, Robert A., additional, Slaugenhaupt, Susan A., additional, Hagège, Albert A., additional, Dina, Christian, additional, Jeunemaitre, Xavier, additional, Milan, David J., additional, Norris, Russell A., additional, and Bouatia-Naji, Nabila, additional

Published
2019
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