190 results on '"Tucker, Nathan R."'
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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
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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
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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)
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Armstrong, Ellie E, Perry, Blair W, Huang, Yongqing, Garimella, Kiran V, Jansen, Heiko T, Robbins, Charles T, Tucker, Nathan R, and Kelley, Joanna L
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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
4. Comparative analysis of two independent Myh6-Cre transgenic mouse lines
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Davenport, Amanda, Kessinger, Chase W., Pfeiffer, Ryan D., Shah, Nikita, Xu, Richard, Abel, E. Dale, Tucker, Nathan R., and Lin, Zhiqiang
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- 2024
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5. SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart
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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
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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
6. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.
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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
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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
7. Transcriptome variation in human tissues revealed by long-read sequencing
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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.
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- 2022
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8. Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy
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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.
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- 2022
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9. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
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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.
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- 2021
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10. Long-range Pitx2c enhancer–promoter interactions prevent predisposition to atrial fibrillation
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Zhang, Min, Hill, Matthew C., Kadow, Zachary A., Suh, Ji Ho, Tucker, Nathan R., Hall, Amelia W., Tran, Tien T., Swinton, Paul S., Leach, John P., Margulies, Kenneth B., Ellinor, Patrick T., Li, Na, and Martin, James F.
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- 2019
11. Loss of the Atrial Fibrillation-Related Gene, Zfhx3 , Results in Atrial Dilation and Arrhythmias
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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
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- 2023
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12. Transcriptional and Cellular Diversity of the Human Heart
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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.
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- 2020
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13. Identification of Functional Variant Enhancers Associated With Atrial Fibrillation
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van Ouwerkerk, Antoinette F., Bosada, Fernanda M., Liu, Jia, Zhang, Juan, van Duijvenboden, Karel, Chaffin, Mark, Tucker, Nathan R., Pijnappels, Daniel, Ellinor, Patrick T., Barnett, Phil, de Vries, Antoine A.F., and Christoffels, Vincent M.
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- 2020
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14. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation
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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.
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- 2020
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15. Cell-Specific Mechanisms in the Heart of COVID-19 Patients
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Tsai, Emily J., primary, Cˇiháková, Daniela, additional, and Tucker, Nathan R., additional
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- 2023
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16. Cardioprotective Effects of MTSS1 Enhancer Variants
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Morley, Michael P., Wang, Xiao, Hu, Ray, Brandimarto, Jeffrey, Tucker, Nathan R., Felix, Janine F., Smith, Nicholas L., van der Harst, Pim, Ellinor, Patrick T., Margulies, Kenneth B., Musunuru, Kiran, and Cappola, Thomas P.
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- 2019
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17. Sex-specific responses to slow progressive pressure overload in a large animal model of HFpEF
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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
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- 2022
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18. COVID-19 and Cardiovascular Disease
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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
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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.
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- 2021
19. Hsp27 Is Persistently Expressed in Zebrafish Skeletal and Cardiac Muscle Tissues but Dispensable for Their Morphogenesis
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Tucker, Nathan R., Ustyugov, Alexey, Bryantsev, Anton L., Konkel, Michael E., and Shelden, Eric. A.
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- 2009
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20. Clinico-histopathologic and single-nuclei RNA-sequencing insights into cardiac injury and microthrombi in critical COVID-19
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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
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- 2022
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21. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism
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Tucker, Nathan R., Clauss, Sebastian, and Ellinor, Patrick T.
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- 2016
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22. Abstract 14422: Molecular Pathogenesis of Cardiac Microthrombi in Fatal Covid-19: Insights from Clinico-histopathologic and Single Nuclei RNA Sequencing Analyses
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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
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- 2021
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23. Abstract 8955: Cardiopulmonary Phenotyping of Sex-Based Differences in a Feline Model of HFpEF
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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
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- 2021
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24. Overexpression of KCNN3 results in sudden cardiac death
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Mahida, Saagar, Mills, Robert W., Tucker, Nathan R., Simonson, Bridget, Macri, Vincenzo, Lemoine, Marc D., Das, Saumya, Milan, David J., and Ellinor, Patrick T.
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- 2014
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25. Beary Good Genome: Haplotype-Resolved, Chromosome-Level Assembly of the Brown Bear (Ursus arctos).
- Author
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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
- Full Text
- View/download PDF
26. Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation
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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
27. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation
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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
28. Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation
- Author
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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
29. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation
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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
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- 2020
30. Epigenetic Analyses of Human Left Atrial Tissue Identifies Gene Networks Underlying Atrial Fibrillation
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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
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- 2020
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31. Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 Mediated Myocarditis
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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
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- 2020
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- View/download PDF
32. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
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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.
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- 2018
33. Genome-Wide Association Study–Driven Gene-Set Analyses, Genetic, and Functional Follow-Up Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse
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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
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- 2019
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34. GWAS-driven Pathway Analyses and Functional Validation Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse
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Yu, Mengyao, primary, Georges, Adrien, additional, Tucker, Nathan R., additional, Kyryachenko, Sergiy, additional, Ellinor, Patrick T., additional, Milan, David J., additional, Norris, Russell (Chip), additional, and Bouatia-Naji, Nabila, additional
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- 2019
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35. Multi-ethnic genome-wide association study for atrial fibrillation
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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, Doerr, 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, Kaeaeb, Stefan, Kahonen, 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, Lehtimaki, 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, Lyytikainen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., Maerz, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Mueller-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, Pare, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribases, 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., Seppala, 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, Theriault, Sebastien, 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, Voelker, 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., Ellinor, Patrick T., 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, Doerr, 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, Kaeaeb, Stefan, Kahonen, 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, Lehtimaki, 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, Lyytikainen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., Maerz, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Mueller-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, Pare, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribases, 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., Seppala, 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, Theriault, Sebastien, 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, Voelker, 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.
- Abstract
Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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- 2018
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36. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval
- Author
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Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, Isaacs, Aaron, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, and Isaacs, Aaron
- Published
- 2018
37. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval
- Author
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Onderzoek Precision medicine, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, Isaacs, Aaron, Onderzoek Precision medicine, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Lin, Honghuang, van Setten, Jessica, Smith, Albert V, Bihlmeyer, Nathan A, Warren, Helen R, Brody, Jennifer A, Radmanesh, Farid, Hall, Leanne, Grarup, Niels, Müller-Nurasyid, Martina, Boutin, Thibaud, Verweij, Niek, Lin, Henry J, Li-Gao, Ruifang, van den Berg, Marten E, Marten, Jonathan, Weiss, Stefan, Prins, Bram P, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Mei, Hao, Harris, Tamara B, Launer, Lenore J, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Connell, John M, Huang, Paul L, Weng, Lu-Chen, Jameson, Heather S, Hucker, William, Hanley, Alan, Tucker, Nathan R, Chen, Yii-Der Ida, Bis, Joshua C, Rice, Kenneth M, Sitlani, Colleen M, Kors, Jan A, Xie, Zhijun, Wen, Chengping, Magnani, Jared W, Nelson, Christopher P, Kanters, Jørgen K, Sinner, Moritz F, Strauch, Konstantin, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Bork-Jensen, Jette, Pedersen, Oluf, Linneberg, Allan, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Yao, Jie, Guo, Xiuqing, Taylor, Kent D, Sotoodehnia, Nona, Rotter, Jerome I, Mook-Kanamori, Dennis O, Trompet, Stella, Rivadeneira, Fernando, Uitterlinden, André, Eijgelsheim, Mark, Padmanabhan, Sandosh, Smith, Blair H, Völzke, Henry, Felix, Stephan B, Homuth, Georg, Völker, Uwe, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Kähönen, Mika, Raitakari, Olli T, Gudnason, Vilmundur, Arking, Dan E, Munroe, Patricia B, Psaty, Bruce M, van Duijn, Cornelia M, Benjamin, Emelia J, Rosand, Jonathan, Samani, Nilesh J, Hansen, Torben, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Jukema, J Wouter, Stricker, Bruno H, Hayward, Caroline, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Wilson, James G, Ellinor, Patrick T, Lubitz, Steven A, and Isaacs, Aaron
- Published
- 2018
38. Erratum: Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation
- Author
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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, R V R Horimoto, Andrea, Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Thériault, Sébastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Choi, Seung Hoan, Weng, Lu-Chen, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J, Shah, Svati H, Sun, Albert, Hopewell, Jemma C, Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B, Paré, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P, Verweij, Niek, 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, Anderson, Christopher D, Taylor, Kent D, Campbell, Archie, Magnusson, Patrik K, Porteous, David, Hocking, Lynne J, Vlachopoulou, Efthymia, Pedersen, Nancy L, Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C, Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W, Heilmann-Heimbach, 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, METASTROKE Consortium of the ISGC, Neurology Working Group of the CHARGE Consortium, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, J F Loos, Ruth, Laurikka, Jari, Conen, David, Rosand, Jonathan, van der Harst, Pim, 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, Kääb, Stefan, Chasman, Daniel I, Heckbert, Susan R, Benjamin, Emelia J, Tanaka, Toshihiro, Lunetta, Kathryn L, Lubitz, Steven A, Ellinor, Patrick T, and AFGen Consortium
- Subjects
Genetics ,Journal Article ,Medizin ,Article - Abstract
Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8
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- 2017
39. Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval
- Author
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Lin, Honghuang, primary, van Setten, Jessica, additional, Smith, Albert V., additional, Bihlmeyer, Nathan A., additional, Warren, Helen R., additional, Brody, Jennifer A., additional, Radmanesh, Farid, additional, Hall, Leanne, additional, Grarup, Niels, additional, Müller-Nurasyid, Martina, additional, Boutin, Thibaud, additional, Verweij, Niek, additional, Lin, Henry J., additional, Li-Gao, Ruifang, additional, van den Berg, Marten E., additional, Marten, Jonathan, additional, Weiss, Stefan, additional, Prins, Bram P., additional, Haessler, Jeffrey, additional, Lyytikäinen, Leo-Pekka, additional, Mei, Hao, additional, Harris, Tamara B., additional, Launer, Lenore J., additional, Li, Man, additional, Alonso, Alvaro, additional, Soliman, Elsayed Z., additional, Connell, John M., additional, Huang, Paul L., additional, Weng, Lu-Chen, additional, Jameson, Heather S., additional, Hucker, William, additional, Hanley, Alan, additional, Tucker, Nathan R., additional, Chen, Yii-Der Ida, additional, Bis, Joshua C., additional, Rice, Kenneth M., additional, Sitlani, Colleen M., additional, Kors, Jan A., additional, Xie, Zhijun, additional, Wen, Chengping, additional, Magnani, Jared W., additional, Nelson, Christopher P., additional, Kanters, Jørgen K., additional, Sinner, Moritz F., additional, Strauch, Konstantin, additional, Peters, Annette, additional, Waldenberger, Melanie, additional, Meitinger, Thomas, additional, Bork-Jensen, Jette, additional, Pedersen, Oluf, additional, Linneberg, Allan, additional, Rudan, Igor, additional, de Boer, Rudolf A., additional, van der Meer, Peter, additional, Yao, Jie, additional, Guo, Xiuqing, additional, Taylor, Kent D., additional, Sotoodehnia, Nona, additional, Rotter, Jerome I., additional, Mook-Kanamori, Dennis O., additional, Trompet, Stella, additional, Rivadeneira, Fernando, additional, Uitterlinden, André, additional, Eijgelsheim, Mark, additional, Padmanabhan, Sandosh, additional, Smith, Blair H., additional, Völzke, Henry, additional, Felix, Stephan B., additional, Homuth, Georg, additional, Völker, Uwe, additional, Mangino, Massimo, additional, Spector, Timothy D., additional, Bots, Michiel L., additional, Perez, Marco, additional, Kähönen, Mika, additional, Raitakari, Olli T., additional, Gudnason, Vilmundur, additional, Arking, Dan E., additional, Munroe, Patricia B., additional, Psaty, Bruce M., additional, van Duijn, Cornelia M., additional, Benjamin, Emelia J., additional, Rosand, Jonathan, additional, Samani, Nilesh J., additional, Hansen, Torben, additional, Kääb, Stefan, additional, Polasek, Ozren, additional, van der Harst, Pim, additional, Heckbert, Susan R., additional, Jukema, J. Wouter, additional, Stricker, Bruno H., additional, Hayward, Caroline, additional, Dörr, Marcus, additional, Jamshidi, Yalda, additional, Asselbergs, Folkert W., additional, Kooperberg, Charles, additional, Lehtimäki, Terho, additional, Wilson, James G., additional, Ellinor, Patrick T., additional, Lubitz, Steven A., additional, and Isaacs, Aaron, additional
- Published
- 2018
- Full Text
- View/download PDF
40. Response by Ma et al to Letter Regarding Article, “Novel Mutation in FLNC (Filamin C) Causes Familial Restrictive Cardiomyopathy”
- Author
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Tucker, Nathan R., primary and Ellinor, Patrick T., additional
- Published
- 2018
- Full Text
- View/download PDF
41. Genetic Reduction in Left Ventricular Protein Kinase C-α and Adverse Ventricular Remodeling in Human Subjects
- Author
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Hu, Ray, primary, Morley, Michael P., additional, Brandimarto, Jeffrey, additional, Tucker, Nathan R., additional, Parsons, Victoria A., additional, Zhao, Sihai D., additional, Meder, Benjamin, additional, Katus, Hugo A., additional, Rühle, Frank, additional, Stoll, Monika, additional, Villard, Eric, additional, Cambien, François, additional, Lin, Honghuang, additional, Smith, Nicholas L., additional, Felix, Janine F., additional, Vasan, Ramachandran S., additional, van der Harst, Pim, additional, Newton-Cheh, Christopher, additional, Li, Jin, additional, Kim, Cecilia E., additional, Hakonarson, Hakon, additional, Hannenhalli, Sridhar, additional, Ashley, Euan A., additional, Moravec, Christine S., additional, Tang, W.H. Wilson, additional, Maillet, Marjorie, additional, Molkentin, Jeffery D., additional, Ellinor, Patrick T., additional, Margulies, Kenneth B., additional, and Cappola, Thomas P, additional
- Published
- 2018
- Full Text
- View/download PDF
42. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation
- Author
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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., Mueller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Doerr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikainen, Leo-Pekka, Seppala, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Theriault, Sebastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Choi, Seung Hoan, Weng, Lu-Chen, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati H., Sun, Albert, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Pare, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, 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., Kahonen, 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, Anderson, Christopher D., Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann-Heimbach, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Voelker, Uwe, Joeckel, 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, Rosand, Jonathan, van der Harst, Pim, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., Maerz, Winfried, Lehtimaki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Kaeaeb, Stefan, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., 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., Mueller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Doerr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikainen, Leo-Pekka, Seppala, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Theriault, Sebastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Choi, Seung Hoan, Weng, Lu-Chen, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati H., Sun, Albert, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Pare, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, 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., Kahonen, 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, Anderson, Christopher D., Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann-Heimbach, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Voelker, Uwe, Joeckel, 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, Rosand, Jonathan, van der Harst, Pim, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., Maerz, Winfried, Lehtimaki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Kaeaeb, Stefan, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., and Ellinor, Patrick T.
- Abstract
Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery(8).
- Published
- 2017
- Full Text
- View/download PDF
43. Long-range Pitx2c enhancer-promoter interactions prevent predisposition to atrial fibrillation.
- Author
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Min Zhang, Hill, Matthew C., Kadow, Zachary A., Ji Ho Suh, Tucker, Nathan R., Hall, Amelia W., Tran, Tien T., Swinton, Paul S., Leach, John P., Margulies, Kenneth B., Ellinor, Patrick T., Na Li, and Martin, James F.
- Subjects
ATRIAL fibrillation ,COMPARATIVE genomics ,KNOCKOUT mice ,ARRHYTHMIA ,CHROMOSOMES - Abstract
Genome-wide association studies found that increased risk for atrial fibrillation (AF), the most common human heart arrhythmia, is associated with noncoding sequence variants located in proximity to PITX2. Cardiomyocyte-specific epigenomic and comparative genomics uncovered 2 AF-associated enhancers neighboring PITX2 with varying conservation in mice. Chromosome conformation capture experiments in mice revealed that the Pitx2c promoter directly contacted the AF-associated enhancer regions. CRISPR/Cas9- mediated deletion of a 20-kb topologically engaged enhancer led to reduced Pitx2c transcription and AF predisposition. Allele-specific chromatin immunoprecipitation sequencing on hybrid heterozygous enhancer knockout mice revealed that long-range interaction of an AF-associated region with the Pitx2c promoter was required for maintenance of the Pitx2c promoter chromatin state. Long-range looping was mediated by CCCTC-binding factor (CTCF), since genetic disruption of the intronic CTCF-binding site caused reduced Pitx2c expression, AF predisposition, and diminished active chromatin marks on Pitx2. AF risk variants located at 4q25 reside in genomic regions possessing long-range transcriptional regulatory functions directed at PITX2. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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44. Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
- Author
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Wang, Xinchen, Tucker, Nathan R., Rizki, Gizem, Mills, Robert, Krijger, Peter Hugo Lodewijk, de Wit, Elzo, Subramanian, Vidya, Bartell, Eric, Nguyen, Xinh Xinh, Ye, Jiangchuan, Leyton-Mange, Jordan, Dolmatova, Elena V., Harst, Pim Van Der, Laat, Wouter De, Ellinor, Patrick T., Newton-Cheh, Christopher, Milan, David J., Kellis, Manolis, Boyer, Laurie A., Wang, Xinchen, Tucker, Nathan R., Rizki, Gizem, Mills, Robert, Krijger, Peter Hugo Lodewijk, de Wit, Elzo, Subramanian, Vidya, Bartell, Eric, Nguyen, Xinh Xinh, Ye, Jiangchuan, Leyton-Mange, Jordan, Dolmatova, Elena V., Harst, Pim Van Der, Laat, Wouter De, Ellinor, Patrick T., Newton-Cheh, Christopher, Milan, David J., Kellis, Manolis, and Boyer, Laurie A.
- Published
- 2016
45. Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
- Author
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Divisie Biomedische Genetica, Hubrecht Institute with UMC, Cancer, Wang, Xinchen, Tucker, Nathan R., Rizki, Gizem, Mills, Robert, Krijger, Peter Hugo Lodewijk, de Wit, Elzo, Subramanian, Vidya, Bartell, Eric, Nguyen, Xinh Xinh, Ye, Jiangchuan, Leyton-Mange, Jordan, Dolmatova, Elena V., Harst, Pim Van Der, Laat, Wouter De, Ellinor, Patrick T., Newton-Cheh, Christopher, Milan, David J., Kellis, Manolis, Boyer, Laurie A., Divisie Biomedische Genetica, Hubrecht Institute with UMC, Cancer, Wang, Xinchen, Tucker, Nathan R., Rizki, Gizem, Mills, Robert, Krijger, Peter Hugo Lodewijk, de Wit, Elzo, Subramanian, Vidya, Bartell, Eric, Nguyen, Xinh Xinh, Ye, Jiangchuan, Leyton-Mange, Jordan, Dolmatova, Elena V., Harst, Pim Van Der, Laat, Wouter De, Ellinor, Patrick T., Newton-Cheh, Christopher, Milan, David J., Kellis, Manolis, and Boyer, Laurie A.
- Published
- 2016
46. Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
- Author
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Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Wang, Xinchen, Rizki, Gizem, Subramanian, Vidya, Bartell, Eric R., Kellis, Manolis, Boyer, Laurie, Mills, Robert, de Wit, Elzo, Nguyen, Xinh-Xinh, Ye, Jiangchuan, Leyton-Mange, Jordan, van der Harst, Pim, de Laat, Wouter, Newton-Cheh, Christopher, Tucker, Nathan R., Krijger, Peter H. L., Dolmatova, Elena V., Ellinor, Patrick T., Milan, David J., Boyer, Laurie Ann, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Wang, Xinchen, Rizki, Gizem, Subramanian, Vidya, Bartell, Eric R., Kellis, Manolis, Boyer, Laurie, Mills, Robert, de Wit, Elzo, Nguyen, Xinh-Xinh, Ye, Jiangchuan, Leyton-Mange, Jordan, van der Harst, Pim, de Laat, Wouter, Newton-Cheh, Christopher, Tucker, Nathan R., Krijger, Peter H. L., Dolmatova, Elena V., Ellinor, Patrick T., Milan, David J., and Boyer, Laurie Ann
- Abstract
Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits.
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- 2016
47. A Functional Variant Associated with Atrial Fibrillation Regulates PITX2c Expression through TFAP2a
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Ye, Jiangchuan, primary, Tucker, Nathan R., additional, Weng, Lu-Chen, additional, Clauss, Sebastian, additional, Lubitz, Steven A., additional, and Ellinor, Patrick T., additional
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- 2016
- Full Text
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48. Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families
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Hanley, Alan, primary, Walsh, Katie A., additional, Joyce, Caroline, additional, McLellan, Michael A., additional, Clauss, Sebastian, additional, Hagen, Amaya, additional, Shea, Marisa A., additional, Tucker, Nathan R., additional, Lin, Honghuang, additional, Fahy, Gerard J., additional, and Ellinor, Patrick T., additional
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- 2016
- Full Text
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49. PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance
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Kiando, Soto Romuald, primary, Tucker, Nathan R., additional, Castro-Vega, Luis-Jaime, additional, Katz, Alexander, additional, D’Escamard, Valentina, additional, Tréard, Cyrielle, additional, Fraher, Daniel, additional, Albuisson, Juliette, additional, Kadian-Dodov, Daniella, additional, Ye, Zi, additional, Austin, Erin, additional, Yang, Min-Lee, additional, Hunker, Kristina, additional, Barlassina, Cristina, additional, Cusi, Daniele, additional, Galan, Pilar, additional, Empana, Jean-Philippe, additional, Jouven, Xavier, additional, Gimenez-Roqueplo, Anne-Paule, additional, Bruneval, Patrick, additional, Hyun Kim, Esther Soo, additional, Olin, Jeffrey W., additional, Gornik, Heather L., additional, Azizi, Michel, additional, Plouin, Pierre-François, additional, Ellinor, Patrick T., additional, Kullo, Iftikhar J., additional, Milan, David J., additional, Ganesh, Santhi K., additional, Boutouyrie, Pierre, additional, Kovacic, Jason C., additional, Jeunemaitre, Xavier, additional, and Bouatia-Naji, Nabila, additional
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- 2016
- Full Text
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50. Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
- Author
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Wang, Xinchen, primary, Tucker, Nathan R, additional, Rizki, Gizem, additional, Mills, Robert, additional, Krijger, Peter HL, additional, de Wit, Elzo, additional, Subramanian, Vidya, additional, Bartell, Eric, additional, Nguyen, Xinh-Xinh, additional, Ye, Jiangchuan, additional, Leyton-Mange, Jordan, additional, Dolmatova, Elena V, additional, van der Harst, Pim, additional, de Laat, Wouter, additional, Ellinor, Patrick T, additional, Newton-Cheh, Christopher, additional, Milan, David J, additional, Kellis, Manolis, additional, and Boyer, Laurie A, additional
- Published
- 2016
- Full Text
- View/download PDF
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