Search

Your search keyword '"Dan M, Roden"' showing total 28 results
Start Over Author "Dan M, Roden" Publisher elsevier
28 results on '"Dan M, Roden"'

1. Cardiac Sarcoidosis and a Likely Pathogenic TTN Variant in a Patient Presenting With Ventricular Tachycardia

Author

Zain M. Virk, MD, T. Lee Richardson, Jr., MD, Joseph F. Nowatzke, MD, Asad Ullah, MD, Dawn M. Pedrotty, MD, M. Benjamin Shoemaker, MD, MSCI, Arvindh Kanagasundram, MD, Dan M. Roden, MD, and William G. Stevenson, MD

Subjects
atrial fibrillation, cardiomyopathy, genetic disorders, imaging, ventricular tachycardia, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Rare variants in TTN are the most common monogenic cause of early-onset atrial fibrillation and dilated cardiomyopathy. Whereas cardiac sarcoidosis is very underdiagnosed, a common presentation can be ventricular arrhythmias. This report presents a patient with a likely pathogenic TTN variant and cardiac sarcoidosis. (Level of Difficulty: Intermediate.)

Published
2023
Full Text
View/download PDF

2. Personalized structural biology reveals the molecular mechanisms underlying heterogeneous epileptic phenotypes caused by de novo KCNC2 variants

Author

Souhrid Mukherjee, Thomas A. Cassini, Ningning Hu, Tao Yang, Bian Li, Wangzhen Shen, Christopher W. Moth, David C. Rinker, Jonathan H. Sheehan, Joy D. Cogan, John H. Newman, Rizwan Hamid, Robert L. Macdonald, Dan M. Roden, Jens Meiler, Georg Kuenze, John A. Phillips, and John A. Capra

Subjects
developmental and epileptic encephalopathy, DEE, KCNC2, de novo variant, molecular dynamics simulations, electrophysiology, Genetics, QH426-470
Abstract

Summary: Whole-exome sequencing (WES) in the clinic has identified several rare monogenic developmental and epileptic encephalopathies (DEE) caused by ion channel variants. However, WES often fails to provide actionable insight for rare diseases, such as DEEs, due to the challenges of interpreting variants of unknown significance (VUS). Here, we describe a “personalized structural biology” (PSB) approach that leverages recent innovations in the analysis of protein 3D structures to address this challenge. We illustrate this approach in an Undiagnosed Diseases Network (UDN) individual with DEE symptoms and a de novo VUS in KCNC2 (p.V469L), the Kv3.2 voltage-gated potassium channel. A nearby KCNC2 variant (p.V471L) was recently suggested to cause DEE-like phenotypes. Computational structural modeling suggests that both affect protein function. However, despite their proximity, the p.V469L variant is likely to sterically block the channel pore, while the p.V471L variant is likely to stabilize the open state. Biochemical and electrophysiological analyses demonstrate heterogeneous loss-of-function and gain-of-function effects, as well as differential response to 4-aminopyridine treatment. Molecular dynamics simulations illustrate that the pore of the p.V469L variant is more constricted, increasing the energetic barrier for K+ permeation, whereas the p.V471L variant stabilizes the open conformation. Our results implicate variants in KCNC2 as causative for DEE and guide the interpretation of a UDN individual. They further delineate the molecular basis for the heterogeneous clinical phenotypes resulting from two proximal pathogenic variants. This demonstrates how the PSB approach can provide an analytical framework for individualized hypothesis-driven interpretation of protein-coding VUS.

Published
2022
Full Text
View/download PDF

3. Protein structure aids predicting functional perturbation of missense variants in SCN5A and KCNQ1

Author

Brett M. Kroncke, Jeffrey Mendenhall, Derek K. Smith, Charles R. Sanders, John A. Capra, Alfred L. George, Jeffrey D. Blume, Jens Meiler, and Dan M. Roden

Subjects
Biotechnology, TP248.13-248.65
Abstract

Rare variants in the cardiac potassium channel KV7.1 (KCNQ1) and sodium channel NaV1.5 (SCN5A) are implicated in genetic disorders of heart rhythm, including congenital long QT and Brugada syndromes (LQTS, BrS), but also occur in reference populations. We previously reported two sets of NaV1.5 (n = 356) and KV7.1 (n = 144) variants with in vitro characterized channel currents gathered from the literature. Here we investigated the ability to predict commonly reported NaV1.5 and KV7.1 variant functional perturbations by leveraging diverse features including variant classifiers PROVEAN, PolyPhen-2, and SIFT; evolutionary rate and BLAST position specific scoring matrices (PSSM); and structure-based features including “functional densities” which is a measure of the density of pathogenic variants near the residue of interest. Structure-based functional densities were the most significant features for predicting NaV1.5 peak current (adj. R2 = 0.27) and KV7.1 + KCNE1 half-maximal voltage of activation (adj. R2 = 0.29). Additionally, use of structure-based functional density values improves loss-of-function classification of SCN5A variants with an ROC-AUC of 0.78 compared with other predictive classifiers (AUC = 0.69; two-sided DeLong test p = .01). These results suggest structural data can inform predictions of the effect of uncharacterized SCN5A and KCNQ1 variants to provide a deeper understanding of their burden on carriers. Keywords: SCN5A, KCNQ1, Function prediction, Protein structure, And protein function

Published
2019
Full Text
View/download PDF

5. Incessant atrial and ventricular tachycardias associated with an SCN5A mutation

Author

Edward P. Walsh, Andrew M. Glazer, John Papagiannis, Svjetlana Tisma-Dupanovic, Dan M. Roden, Prince J. Kannankeril, Tao Yang, Dimosthenis Avramidis, and Sami Viskin

Subjects
Quinidine, medicine.medical_specialty, Scn5a gene, business.industry, medicine.medical_treatment, Sodium channel mutation, Atrial tachycardia, Catheter ablation, Case Report, Ventricular tachycardia, medicine.disease, Internal medicine, medicine, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, medicine.drug
Published
2021

6. Practical considerations in genomic decision support: The eMERGE experience

Author

Timothy M Herr, Suzette J Bielinski, Erwin Bottinger, Ariel Brautbar, Murray Brilliant, Christopher G Chute, Beth L Cobb, Joshua C Denny, Hakon Hakonarson, Andrea L Hartzler, George Hripcsak, Joseph Kannry, Isaac S Kohane, Iftikhar J Kullo, Simon Lin, Shannon Manzi, Keith Marsolo, Casey Lynnette Overby, Jyotishman Pathak, Peggy Peissig, Jill Pulley, James Ralston, Luke Rasmussen, Dan M Roden, Gerard Tromp, Timothy Uphoff, Chunhua Weng, Wendy Wolf, Marc S Williams, and Justin Starren

Subjects
Clinical decision support, genomic medicine, personalized health care, pharmacogenomics, precision medicine, Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214
Abstract

Background: Genomic medicine has the potential to improve care by tailoring treatments to the individual. There is consensus in the literature that pharmacogenomics (PGx) may be an ideal starting point for real-world implementation, due to the presence of well-characterized drug-gene interactions. Clinical Decision Support (CDS) is an ideal avenue by which to implement PGx at the bedside. Previous literature has established theoretical models for PGx CDS implementation and discussed a number of anticipated real-world challenges. However, work detailing actual PGx CDS implementation experiences has been limited. Anticipated challenges include data storage and management, system integration, physician acceptance, and more. Methods: In this study, we analyzed the experiences of ten members of the Electronic Medical Records and Genomics (eMERGE) Network, and one affiliate, in their attempts to implement PGx CDS. We examined the resulting PGx CDS system characteristics and conducted a survey to understand the unanticipated implementation challenges sites encountered. Results: Ten sites have successfully implemented at least one PGx CDS rule in the clinical setting. The majority of sites elected to create an Omic Ancillary System (OAS) to manage genetic and genomic data. All sites were able to adapt their existing CDS tools for PGx knowledge. The most common and impactful delays were not PGx-specific issues. Instead, they were general IT implementation problems, with top challenges including team coordination/communication and staffing. The challenges encountered caused a median total delay in system go-live of approximately two months. Conclusions: These results suggest that barriers to PGx CDS implementations are generally surmountable. Moreover, PGx CDS implementation may not be any more difficult than other healthcare IT projects of similar scope, as the most significant delays encountered were not unique to genomic medicine. These are encouraging results for any institution considering implementing a PGx CDS tool, and for the advancement of genomic medicine.

Published
2015
Full Text
View/download PDF

7. Genomic Medicine Year in Review: 2019

Author

Eric D. Green, Dan M. Roden, Gail P. Jarvik, Patricia A. Deverka, Teri A. Manolio, Robb Rowley, Mary V. Relling, Cecelia P. Tamburro, Marc S. Williams, George A. Mensah, Geoffrey S. Ginsburg, Rex L. Chisholm, Carol J. Bult, and Howard L. McLeod

Subjects
medicine.medical_specialty, business.industry, Year in review, Family medicine, Genetics, MEDLINE, Medicine, Genomic medicine, Year in Review, business, Genetics (clinical)
Published
2019

8. Contributors

Author

Philip Aagaard, Dominic James Abrams, Hugues Abriel, Wayne O. Adkisson, Esperanza Agullo-Pascual, Francisco J. Alvarado, Ahmad S. Amin, Charles Antzelevitch, Justus M.B. Anumonwo, Luciana Armaganijan, Arash Arya, Samuel Asirvatham, Felipe Atienza, Peter H. Backx, Lisa M. Ballou, Elise Balse, Sujata Balulad, Andrea Barbuti, Gust H. Bardy, Guillaume Bassil, David G. Benditt, Omer Berenfeld, Donald M. Bers, Ofer Binah, Frank Bogun, Rossana Bongianino, Noel G. Boyle, Patrick M. Boyle, Günter Breithardt, Marisa Brini, Peter R. Brink, Pedro Brugada, Eric Buch, Feliksas F. Bukauskas, Hugh Calkins, David J. Callans, Sean M. Caples, Ernesto Carafoli, William A. Catterall, Marina Cerrone, Arnaud Chaumeil, Caressa Chen, Lan S. Chen, Peng-Sheng Chen, Jianding Cheng, Nipavan Chiamvimonvat, David J. Christini, Aman Chugh, Andreu M. Climent, Ira S. Cohen, Stuart J. Connolly, Lebron Cooper, Eric M. Crespo, Lia Crotti, Thomas A. Csepe, Frank Cuoco, Anne B. Curtis, Ralph J. Damiano, Dawood Darbar, Mithilesh K. Das, Andre d’Avila, Mario Delmar, Eva Delpón, Marco Denegri, Arnaud Denis, Nicolas Derval, Isabelle Deschênes, Abhishek Deshmukh, Luigi Di Biase, Timm M. Dickfeld, Hans Dierckx, Borislav Dinov, Sanjay Dixit, Dobromir Dobrev, Remi Dubois, Lars Eckardt, Andrew G. Edwards, Kenneth A. Ellenbogen, Patrick T. Ellinor, N.A. Mark Estes, Larissa Fabritz, Vadim V. Fedorov, Antonio B. Fernandez, Elvis Teijeira Fernández, David Filgueiras-Rama, Michael C. Fishbein, Glenn I. Fishman, David S. Frankel, Paul Friedman, Antonio Frontera, Apoor S. Gami, Paul Garabelli, Alfred L. George, Edward P. Gerstenfeld, Sigfus Gizurarson, Michael R. Gold, Jeffrey J. Goldberger, Andrew Grace, Guido Grassi, Ruth Ann Greenfield, Wendy L. Gross, Blair P. Grubb, María S. Guillem, Sándor Györke, Michel Haïssaguerre, Johan Hake, Henry R. Halperin, Brian J. Hansen, Stéphane Hatem, David L. Hayes, Jordi Heijman, Todd J. Herron, Gerhard Hindricks, Mélèze Hocini, Stefan H. Hohnloser, David R. Holmes, Masahiko Hoshijima, Thomas J. Hund, Mathew D. Hutchinson, Leonard Ilkhanoff, Jodie Ingles, James E. Ip, Warren M. Jackman, Nicholas Jackson, Pierre Jaïs, José Jalife, Bong Sook Jhun, Roy M. John, Monique Jongbloed, Luc Jordaens, Jonathan M. Kalman, Timothy J. Kamp, Mohamed H. Kanj, Suraj Kapa, Beverly Karabin, Ioannis Karakikes, Demosthenes G. Katritsis, Kuljeet Kaur, Paulus Kirchhof, André G. Kléber, George J. Klein, Peter Kohl, Jayanthi N. Koneru, Jacob S. Koruth, Andrew D. Krahn, Trine Krogh-Madsen, Karl Heinz Kuck, Saurabh Kumar, Alexander Kushnir, Neal K. Lakdawala, Zachary W.M. Laksman, Rakesh Latchamsetty, Dennis H. Lau, Bruce B. Lerman, Richard Z. Lin, Shien-Fong Lin, Mark S. Link, Bin Liu, Christopher F. Liu, Deborah J. Lockwood, Anatoli N. Lopatin, Steven A. Lubitz, Rajiv Mahajan, Jonathan C. Makielski, Marek Malik, Francis E. Marchlinski, Steven M. Markowitz, Barry J. Maron, Martin S. Maron, Steven O. Marx, Stéphane Massé, Andrew D. McCulloch, Pippa McKelvie-Sebileau, Spencer J. Melby, Andreas Metzner, Anushka P. Michailova, Gregory F. Michaud, John M. Miller, Jyotsna Mishra, Raul D. Mitrani, Peter J. Mohler, Fred Morady, Robert J. Myerburg, Hiroshi Nakagawa, Chrishan Joseph Nalliah, Kumaraswamy Nanthakumar, Carlo Napolitano, Sanjiv M. Narayan, Andrea Natale, Stanley Nattel, Saman Nazarian, Thao P. Nguyen, Akihiko Nogami, Sami F. Noujaim, Karine Nubret Le Coniat, Brian Olshansky, Jin O-Uchi, Gavin Y. Oudit, Feifan Ouyang, Cevher Ozcan, Douglas L. Packer, Sandeep V. Pandit, Alexander V. Panfilov, David S. Park, Bence Patocskai, Dainius H. Pauza, Neringa Pauziene, Jonathan P. Piccini, Geoffrey S. Pitt, Sunny S. Po, Abhiram Prasad, Silvia G. Priori, Przemysław B. Radwański, Wouter-Jan Rappel, Michelle Reiser, Alejandro Jimenez Restrepo, Richard B. Robinson, Dan M. Roden, Michael R. Rosen, Raphael Rosso, Yoram Rudy, Kristina Rysevaite-Kyguoliene, Hani N. Sabbah, Frederic Sacher, Frank B. Sachse, Ardan M. Saguner, Prashanthan Sanders, Michael C. Sanguinetti, Pasquale Santangeli, Mohammad Sarraf, Jonathan Satin, Martin Jan Schalij, Benjamin J. Scherlag, Matthew R. Schill, J. William Schleifer, Richard B. Schuessler, Peter J. Schwartz, Timon Seeger, Christopher Semsarian, Gino Seravalle, Ashok J. Shah, Robin M. Shaw, Mark J. Shen, Win–Kuang Shen, Shey-Shing Sheu, Kalyanam Shivkumar, Jennifer N.A. Silva, Allan C. Skanes, Kyoko Soejima, Virend K. Somers, Dan Sorajja, Stavros Stavrakis, Christian Steinberg, Lynne Warner Stevenson, William G. Stevenson, Michael O. Sweeney, Charles Swerdlow, Masateru Takigawa, Juan Tamargo, Harikrishna Tandri, Usha B. Tedrow, Nathaniel Thompson, Paul D. Thompson, Gordon F. Tomaselli, Jeffrey A. Towbin, Natalia A. Trayanova, Martin Tristani-Firouzi, Zian H. Tseng, Akiko Ueda, Héctor H. Valdivia, Virginijus Valiunas, Christian van der Werf, George F. Van Hare, David Vidmar, Sami Viskin, Niels Voigt, Edward P. Walsh, Paul J. Wang, Xander H.T. Wehrens, Mark S. Weiss, Arthur A.M. Wilde, Bruce L. Wilkoff, Y. Joseph Woo, Joseph C. Wu, Raymond Yee, Junaid A.B. Zaman, Manuel Zarzoso, Emily P. Zeitler, Katja Zeppenfeld, Tarek Zghaib, Xiao-Dong Zhang, and Douglas P. Zipes

Published
2018
Full Text
View/download PDF

9. List of Contributors

Author

Michael J. Ackerman, Brian H. Annex, Johan Martijn Bos, Wendy K. Chung, Ayotunde O. Dokun, Jennifer L. Hall, Robert A. Hegele, Sekar Kathiresan, Thorsten Kessler, Steven J. Kittner, William E. Kraus, Matthew B. Lanktree, Josephine H. Li, Braxton D. Mitchell, Patricia B. Munroe, Lori A. Orlando, Mihai V. Podgoreanu, Daniel J. Rader, Dan M. Roden, Steven Rosenberg, Christian T. Ruff, Marc S. Sabatine, Heribert Schunkert, Simon von Ameln, Deepak Voora, Helen R. Warren, James A. Wingrove, and Rebekah R. Wu

Published
2018
Full Text
View/download PDF

11. Adverse Drug Events

Author

Dan M. Roden

Subjects
Drug, Gene by environment, medicine.medical_specialty, Drug Prescribing, Drug disposition, Drug elimination, business.industry, media_common.quotation_subject, Drug administration, Pharmacology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Adverse drug event, 030220 oncology & carcinogenesis, Medicine, Medical prescription, business, Intensive care medicine, media_common
Abstract

In this chapter, the term “adverse drug event” (ADE), rather than “reaction,” is used to emphasize the occurrences that are usually multifactorial and often include both biologic and system issues. No drug is free of ADE risk, and prescription of a drug therefore requires the physician to estimate that the risks of therapy are outweighed by the benefits. The list of ADEs for any given drug, let alone for all drugs commonly used by one practitioner, is enormous, and so the problem of ADEs presents challenges not only in guiding prescriptions to maximize benefit and minimize risk but also in educating health practitioners in making such judgments in an increasingly complex molecular and genetic environment. Clearly, information tools play an increasing role in future drug prescribing. The chapter briefly explains the types of ADEs such as system errors, linking events to drug administration—the “easy” examples, linking events to drug administration—the “hard” examples, and many more. Furthermore, it also explains drug interactions that are especially likely to cause ADEs because they inhibit specific pathways for drug elimination. In this situation, ADEs are likely if a second “high-risk” drug using that pathway is also administered.

Published
2017
Full Text
View/download PDF

12. List of Contributors

Author

Salim Abdool Karim, Donna K. Arnett, James R. Baker, Seema Basu, Stacey Berg, Gordon R. Bernard, Italo Biaggioni, Lisa Bomgaars, Robert A. Branch, Nancy J. Brown, Robert M. Califf, Henry C. Chueh, Steven A. Claas, William F. Crowley, Joann Data, George D. Demetri, Zeruesenay Desta, Ruth M. Dunne, Luigi Ferrucci, David A. Flockhart, Audrey Gassman, Rashmi Gopal-Srivastava, Glenn Gormley, Steven Grinspoon, Stephen C. Groft, Katherine E. Hartmann, Elizabeth Heitman, Christopher D. Herrick, Hylton V. Joffe, Kush Kapur, Mark D. Kellogg, Richard B. Kim, Bruce R. Korf, Greg Koski, Ronald L. Krall, Jessica Lasky-Su, Shawn N. Murphy, Christine Nguyen, Ailbhe C. O'Neill, Daniel J. Pallin, James Quinn, Keren Regev, Uwe E. Reinhardt, Todd W. Rice, Rose Marie Robertson, David Robertson, Dan M. Roden, Angela J. Rogers, Daniel E. Salazar, J. Sanford Schwartz, Alan F. Schatzberg, Ellen W. Seely, Joe V. Selby, César Serrano, Donald C. Simonson, Ann R. Stark, Stephanie Studenski, Clare M. Tempany, Marcia A. Testa, Thommey P. Thomas, Rommel G. Tirona, Stephanie L. Tomasic, Suzie Upton, Sten H. Vermund, Brent B. Ward, Howard L. Weiner, Scott T. Weiss, Danielle M. Whicher, Gordon H. Williams, Mary Woolley, and Nathalie K. Zgheib

Published
2017
Full Text
View/download PDF

14. Contributors

Author

Hugues Abriel, Wayne O. Adkisson, Esperanza Agullo-Pascual, Olujimi A. Ajijola, Amin Al-Ahmad, Oluseun Alli, Robert K. Altman, Elad Anter, Charles Antzelevitch, Justus M.B. Anumonwo, Luciana Armaganijan, Hiroshi Ashikaga, Felipe Atienza, Uma Mahesh R. Avula, Peter H. Backx, Elise Balse, Conor D. Barrett, David G. Benditt, Omer Berenfeld, Donald M. Bers, Charles I. Berul, A. Christian Blank, Raffaella Bloise, Frank Matthias Bogun, Martin Borggrefe, Noel G. Boyle, Günter Breithardt, Marisa Brini, Peter R. Brink, Josep Brugada, Pau Brugada, Pedro Brugada, Ramon Brugada, Victoria Brugada, Eric Buch, Feliksas F. Bukauskas, J. David Burkhardt, Nenad Bursac, Hugh Calkins, David J. Callans, Oscar Campuzano, Sean M. Caples, Ernesto Carafoli, Augustin Castellanos, William Catterall, Marina Cerrone, Lan S. Chen, Lei Chen, Peng-Sheng Chen, Ashley Chin, Aman Chugh, Ira S. Cohen, Stuart J. Connolly, Jason Constantino, Lia Crotti, Frank A. Cuoco, Anne B. Curtis, Ralph J. Damiano, Dawood Darbar, Mithilesh K. Das, Mario Delmar, Eva Delpón, Luigi Di Biase, Sanjay Dixit, Dobromir Dobrev, Derek J. Dosdall, John W. Dyer, Lars Eckardt, Andrew G. Edwards, Igor R. Efimov, Kenneth A. Ellenbogen, Patrick T. Ellinor, Emilia Entcheva, N.A. Mark Estes, Rodolphe Fischmeister, John D. Fisher, Glenn I. Fishman, David S. Frankel, Michael R. Franz, Paul A. Friedman, Victor F. Froelicher, Apoor S. Gami, Alfred L. George, Edward P. Gerstenfeld, Michael R. Gold, Jeffrey J. Goldberger, Eleonora Grandi, Richard A. Gray, William J. Groh, Blair P. Grubb, Michel Haissaguerre, Johan Hake, Henry R. Halperin, Louise Harris, Stéphane Hatem, David L. Hayes, Meleze Hocini, Stefan H. Hohnloser, David Richard Holmes, Masahiko Hoshijima, Yuxuan Hu, Thomas J. Hund, Mathew D. Hutchinson, Hye Jin Hwang, Raymond E. Ideker, Leonard Ilkhanoff, Jodie Ingles, Warren M. Jackman, Pierre Jais, José Jalife, Bong Sook Jhun, Roy M. John, Monique Jongbloed, Mark E. Josephson, Alan H. Kadish, Jérôme Kalifa, Jonathan M. Kalman, Timothy J. Kamp, Mohamed Hani Kanj, Beverly Karabin, Robert S. Kass, Demosthenes G. Katritsis, Kuljeet Kaur, Jong J. Kim, Paulus Kirchhof, André G. Kléber, George J. Klein, Peter Kohl, Aravindan Kolandaivelu, Andrew D. Krahn, Andrew Krumerman, Saurabh Kumar, Karl-Heinz Kuck, Edward G. Lakatta, Rakesh Latchamsetty, Dennis H. Lau, Bruce B. Lerman, Jérôme Leroy, William R. Lewis, Shien-Fong Lin, Mark S. Link, Christopher F. Liu, Deborah J. Lockwood, Peter Loh, Anatoli N. Lopatin, John C. Lopshire, Steven A. Lubitz, Christopher Madias, Aman Mahajan, Jonathan C. Makielski, Marek Malik, Victor A. Maltsev, Francis E. Marchlinski, Ariane J. Marelli, Steven M. Markowitz, Barry J. Maron, Jeffrey R. Martens, Steven O. Marx, Andrew D. McCulloch, Andreas Metzner, Anuska P. Michailova, John Michael Miller, Michelle Lynne Milstein, Peter Mohler, Fred Morady, Robert J. Myerburg, Hiroshi Nakagawa, Carlo Napolitano, Sanjiv M. Narayan, Andrea Natale, Stanley Nattel, Saman Nazarian, Jeanne M. Nerbonne, Fu Siong Ng, Akihiko Nogami, Sami F. Noujaim, Brian Olshansky, Hakan Oral, Jin O-Uchi, Feifan Ouyang, Cevher Ozcan, Douglas L. Packer, Olle Pahlm, Sandeep V. Pandit, David S. Park, Geoffrey S. Pitt, Sunny S. Po, Silvia G. Priori, Wouter-Jan Rappel, Vivek Y. Reddy, Jason O. Robertson, Richard B. Robinson, Dan M. Roden, Robert A. Rose, Michael R. Rosen, Raphael Rosso, Yoram Rudy, Jeremy N. Ruskin, Hani N. Sabbah, Frank B. Sachse, Lindsey L. Saint, Javier Saiz, José A. Sánchez-Chapula, Prashanthan Sanders, Michael C. Sanguinetti, Pasquale Santangeli, Georgia Sarquella-Brugada, Jonathan Satin, Martin Jan Schalij, Benjamin J. Scherlag, Rainer Schimpf, Georg Schmidt, Peter J. Schwartz, Christopher Semsarian, Ashok J. Shah, Robin Shaw, Shey Shing Sheu, Kalyanam Shivkumar, Allan C. Skanes, Virend K. Somers, Bruce S. Stambler, Adam B. Stein, Lynne Warner Stevenson, William G. Stevenson, Jian Sun, Richard Sutton, Michael O. Sweeney, Charles Swerdlow, Juan Tamargo, Harikrishna Tandri, Rabi Tawil, Usha Tedrow, Cecile Terrenoire, Catalina Tobón, Jeffrey A. Towbin, Natalia A. Trayanova, Martin Tristani-Firouzi, Richard G. Trohman, Zian H. Tseng, Mintu P. Turakhia, Ravi Vaidyanathan, Héctor H. Valdivia, Virginijus Valiunas, Marcel A.G. van der Heyden, Christian van der Werf, George F. Van, Marmar Vaseghi, Christian Veltmann, Victoria L. Vetter, Sami Viskin, Niels Voigt, Marc A. Vos, Galen S. Wagner, Paul J. Wang, Rukshen Weerasooriya, Arthur A.M. Wilde, Bruce L. Wilkoff, Erik Wissner, Y. Joseph Woo, Masatoshi Yamazaki, Felix Yang, Yael Yaniv, Sing-Chien Yap, Raymond Yee, Manuel Zarzoso, Katja Zeppenfeld, and Douglas P. Zipes

Published
2014
Full Text
View/download PDF

15. Contributors

Author

Raushan Abdula, Michael J. Ackerman, Masood Akhtar, Rishi Anand, Kelley Anderson, Charles Antzelevitch, Angelo Auricchio, Nitish Badhwar, Shane Bailey, Conor D. Barrett, Antonio Bayes de Luna, Paul Belk, David G. Benditt, Begoña Benito, Matthew T. Bennett, Saroja Bharati, David B. Bharucha, William J. Bonney, Neil E. Bowles, Penelope A. Boyden, Babak Bozorgnia, Günter Breithardt, Josep Brugada, Pedro Brugada, Ramon Brugada, Thomas Adam Burkart, J. David Burkhardt, Hugh Calkins, A. John Camm, Franco Cecchi, Marina Cerrone, Nipon Chattipakorn, Shih-Ann Chen, Alexandru B. Chicos, Indrajit Choudhuri, Sebastien Clauss, Jamie Beth Conti, Jonathan M. Cordeiro, Bettina F. Cuneo, Shane R. Cunha, Anne B. Curtis, Michael J. Cutler, Iwona Cygankiewicz, Ralph J. Damiano, James P. Daubert, Jean-Claude Daubert, D. Wyn Davies, Prakash Deedwania, Paul J. DeGroot, Nicolas Derval, Luigi Di Biase, Timm-Michael Dickfeld, Dobromir Dobrev, Michael Domanski, Paul Dorian, Hiten Doshi, Heather S. Duffy, Lars Eckardt, David Eisner, Kenneth A. Ellenbogen, Perry M. Elliott, Nabil El-Sherif, Sabine Ernst, N.A. Mark Estes, Michael D. Ezekowitz, John D. Fisher, Glenn I. Fishman, Andrei Forclaz, G. Joseph Gallinghouse, Ann C. Garlitski, Edward P. Gerstenfeld, Jaswinder Gill, Anne M. Gillis, Jason A. Goebel, Michael R. Gold, Pamela S.N. Goldman, Nora Goldschlager, Lorne J. Gula, Michel Haïssaguerre, John-John Hamel, Donald D. Hegland, Douglas Hettrick, Siew Yen Ho, Mélèze Hocini, Munther K. Homoud, Rodney Horton, Jose F. Huizar, Thomas J. Hund, Raymond E. Ideker, Ramesh Iyer, Kevin P. Jackson, Amir Jadidi, Pierre Jaïs, José Jalife, Michiel Janse, Luc Jordaens, Werner Jung, Stefan Kääb, Alan H. Kadish, Jonathan M. Kalman, Bharat K. Kantharia, Karoly Kaszala, Demosthenes G. Katritsis, Elizabeth S. Kaufman, Susan S. Kim, Senthil Kirubakaran, George J. Klein, Helmut Klein, Sébastien Knecht, Bradley Knight, Paul Knops, Jacob S. Koruth, Peter R. Kowey, Andrew D. Krahn, Andrew Krumerman, Vikas Kuriachan, Fred Kusumoto, Joel A. Lardizabal, Chu-Pak Lau, David H. Lau, Ralph Lazzara, Anson M. Lee, Peter Leong-Sit, Samuel Levy, Thorsten Lewalter, Hua Li, Bruce D. Lindsay, Nick W.F. Linton, Nandini Madan, Yousuf Mahomed, Louisa Malcolme-Lawes, Frank Marchlinski, Barry J. Maron, Ruth McBride, William J. McKenna, Rahul Mehra, Anjlee M. Mehta, John M. Miller, L. Brent Mitchell, Peter J. Mohler, Carlos A. Morillo, Alison R. Muir, Shisuke Myazaki, Robert J. Myerburg, Gerald V. Naccarelli, Rangadham Nagarakanti, Navin C. Nanda, Carlo Napolitano, Andrea Natale, Stanley Nattel, Isabelle Nault, Sami F. Noujaim, Iacopo Olivotto, Heyder Omran, Luigi Padeletti, Richard L. Page, David S. Park, Mark Preminger, Silvia G. Priori, Kara J. Quan, Satish R. Raj, John Rawlins, Shakeeb Razak, Shantanu Reddy, Vivek Y. Reddy, Robert W. Rho, Larry A. Rhodes, Abel Rivero, Melissa Robinson, Dionyssios Robotis, Dan M. Roden, Michael J. Root, Michael R. Rosen, David Rosenbaum, Jeremy Ruskin, Frédéric Sacher, Scott Sakaguchi, Sanjeev Saksena, Javier Sanchez, Pasquale Santageli, Irina Savelieva, Mark H. Schoenfeld, Peter J. Schwartz, Robert Schweikert, Oliver R. Segal, Dipen Shah, Maully Shah, Arjun Sharma, Sanjay Sharma, Robert S. Sheldon, Kaori Shinagawa, Bramah N. Singh, Steven Singh, Chung-Wah Siu, Nicholas D. Skadsberg, Allan C. Skanes, April Slee, Jasbir Sra, Gerhard Steinbeck, David Steinhaus, William G. Stevenson, Janette F. Strasburger, Raymond W. Sy, Andrew W. Teh, David J. Tester, Gordon Tomaselli, Jeffrey A. Towbin, Jacques Turgeon, Gioia Turitto, Wendy Tzou, J. Gert van Dijk, George F. Van Hare, Nathan Van Houzen, Matteo Vatta, Vasanth Vedantham, Victoria L. Vetter, Rochus K. Voeller, Galen Wagner, Reza Wakili, Mariah L. Walker, Paul J. Wang, Andrew L. Wit, Matthew Wright, Raymond Yee, Jason D. Zagrodsky, Wojciech Zareba, Stephan Zellerhoff, and Paul Ziegler

Published
2012
Full Text
View/download PDF

16. Contributors

Author

William T. Abraham, Michael A. Acker, Michael J. Ackerman, Philip A. Ades, Elliott M. Antman, Piero Anversa, Gary J. Balady, Kenneth L. Baughman, Joshua Beckman, Michael A. Bettmann, Deepak L. Bhatt, William E. Boden, Robert O. Bonow, Eugene Braunwald, Alan C. Braverman, J. Douglas Bremner, Hugh Calkins, Christopher P. Cannon, John M. Canty, Agustin Castellanos, Bernard R. Chaitman, Ming Hui Chen, Heidi M. Connolly, Mark A. Creager, Edécio Cunha-Neto, Charles J. Davidson, Vasken Dilsizian, Stefanie Dimmeler, Pamela S. Douglas, Andrew C. Eisenhauer, Linda L. Emanuel, Edzard Ernst, James C. Fang, G. Michael Felker, Gerasimos S. Filippatos, Stacy D. Fisher, Lee A. Fleisher, Thomas Force, J. Michael Gaziano, Thomas A. Gaziano, Jacques Genest, Mihai Gheorghiade, Ary L. Goldberger, Samuel Z. Goldhaber, Larry B. Goldstein, Richard J. Gray, Barry Greenberg, Bartley P. Griffith, William J. Groh, Joshua M. Hare, Gerd Hasenfuss, David L. Hayes, Maria de Lourdes Higuchi, L. David Hillis, Farouc A. Jaffer, Mariell Jessup, Andrew M. Kahn, Jan Kajstura, Norman M. Kaplan, Adolf W. Karchmer, Irwin Klein, Harlan M. Krumholz, Raymond Y. Kwong, Philippe L. L’Allier, Richard A. Lange, Thomas H. Lee, Annarosa Leri, Martin M. LeWinter, Peter Libby, Steven E. Lipshultz, Peter Liu, Brian F. Mandell, Douglas L. Mann, Barry J. Maron, Kenneth L. Mattox, Peter A. McCullough, Darren K. McGuire, Bruce McManus, Mandeep R. Mehra, John M. Miller, David M. Mirvis, Fred Morady, David A. Morrow, Dariush Mozaffarian, Paul S. Mueller, Robert J. Myerburg, Elizabeth G. Nabel, L. Kristin Newby, Patrick T. O’Gara, Jae K. Oh, Jeffrey Olgin, Lionel H. Opie, Catherine M. Otto, Jeffrey J. Popma, Reed E. Pyeritz, B. Soma Raju, José A.F. Ramires, Margaret M. Redfield, Andrew N. Redington, Stuart Rich, Paul M Ridker, Dan M. Roden, Michael Rubart, Marc S. Sabatine, Luis A. Sanchez, Janice B. Schwartz, Christine E. Seidman, J.G. Seidman, Dhun H. Sethna, Jeffrey F. Smallhorn, Virend K. Somers, Andrei C. Sposito, Charles D. Swerdlow, Jean-Claude Tardif, Allen J. Taylor, David J. Tester, Judith Therrien, Paul D. Thompson, Robert W. Thompson, Marc D. Tischler, Peter I. Tsai, Zoltan G. Turi, James E. Udelson, Viola Vaccarino, Ronald G. Victor, Alexandra Villa-Forte, Matthew J. Wall, Carole A. Warnes, Gary D. Webb, John G. Webb, Ralph Weissleder, Jeffrey I. Weitz, Christopher J. White, Stephen D. Wiviott, Clyde W. Yancy, Andreas M. Zeiher, and Douglas P. Zipes

Published
2012
Full Text
View/download PDF

19. Variants Near FOXE1 Are Associated with Hypothyroidism and Other Thyroid Conditions: Using Electronic Medical Records for Genome- and Phenome-wide Studies

Author

Iftikhar J. Kullo, Joshua C. Denny, Catherine A. McCarty, Jyotishman Pathak, Noah Weston, Dan M. Roden, Rongling Li, Yuki Bradford, Jennifer A. Pacheco, Lisa Bastarache, Rex L. Chisholm, Martha E. Matsumoto, M. Geoffrey Hayes, Mariza de Andrade, Luke V. Rasmussen, Christopher G. Chute, Russell A. Wilke, Peggy L. Peissig, High Seng Chai, Rebecca L. Zuvich, Peter Kopp, Daniel R. Masys, David Carrell, Dana C. Crawford, Katherine M. Newton, Suzette J. Bielinski, Xiaoming Wang, Gail P. Jarvik, Melissa A. Basford, Abel N. Kho, Marylyn D. Ritchie, Eric B. Larson, Andrea H. Ramirez, and Teri A. Manolio

Subjects
Genetic Markers, Male, Linkage disequilibrium, medicine.medical_specialty, Genotype, Medical Records Systems, Computerized, Graves' disease, Population, Single-nucleotide polymorphism, Genome-wide association study, Bioinformatics, Article, 03 medical and health sciences, 0302 clinical medicine, Hypothyroidism, Predictive Value of Tests, Internal medicine, Genetics, Medicine, Humans, Genetics(clinical), education, Genetics (clinical), 030304 developmental biology, Aged, 0303 health sciences, education.field_of_study, Genome, business.industry, Thyroid disease, Primary hypothyroidism, Genetic Variation, Forkhead Transcription Factors, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Phenotype, 030220 oncology & carcinogenesis, Female, business, Algorithms, Genome-Wide Association Study
Abstract

We repurposed existing genotypes in DNA biobanks across the Electronic Medical Records and Genomics network to perform a genome-wide association study for primary hypothyroidism, the most common thyroid disease. Electronic selection algorithms incorporating billing codes, laboratory values, text queries, and medication records identified 1317 cases and 5053 controls of European ancestry within five electronic medical records (EMRs); the algorithms' positive predictive values were 92.4% and 98.5% for cases and controls, respectively. Four single-nucleotide polymorphisms (SNPs) in linkage disequilibrium at 9q22 near FOXE1 were associated with hypothyroidism at genome-wide significance, the strongest being rs7850258 (odds ratio [OR] 0.74, p = 3.96 × 10(-9)). This association was replicated in a set of 263 cases and 1616 controls (OR = 0.60, p = 5.7 × 10(-6)). A phenome-wide association study (PheWAS) that was performed on this locus with 13,617 individuals and more than 200,000 patient-years of billing data identified associations with additional phenotypes: thyroiditis (OR = 0.58, p = 1.4 × 10(-5)), nodular (OR = 0.76, p = 3.1 × 10(-5)) and multinodular (OR = 0.69, p = 3.9 × 10(-5)) goiters, and thyrotoxicosis (OR = 0.76, p = 1.5 × 10(-3)), but not Graves disease (OR = 1.03, p = 0.82). Thyroid cancer, previously associated with this locus, was not significantly associated in the PheWAS (OR = 1.29, p = 0.09). The strongest association in the PheWAS was hypothyroidism (OR = 0.76, p = 2.7 × 10(-13)), which had an odds ratio that was nearly identical to that of the curated case-control population in the primary analysis, providing further validation of the PheWAS method. Our findings indicate that EMR-linked genomic data could allow discovery of genes associated with many diseases without additional genotyping cost.

Published
2011

20. Robust Replication of Genotype-Phenotype Associations across Multiple Diseases in an Electronic Medical Record

Author

Dana C. Crawford, Jill M. Pulley, Jonathan L. Haines, Kristin Brown-Gentry, Daniel R. Masys, Dan M. Roden, Justin B. Weiner, Andrea H. Ramirez, Melissa A. Basford, Joshua C. Denny, Marylyn D. Ritchie, and Jeffrey R. Balser

Subjects
Multiple Sclerosis, Genotype, Genotype-Phenotype Association, Single-nucleotide polymorphism, Genome-wide association study, Disease, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Article, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Atrial Fibrillation, Replication (statistics), Genetics, Electronic Health Records, Humans, Medicine, Genetics(clinical), 030212 general & internal medicine, Genetic Association Studies, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Genome, Human, business.industry, Electronic medical record, Correction, DNA, Odds ratio, Biobank, Human genetics, 3. Good health, Phenotype, Biorepository, Diabetes Mellitus, Type 2, Case-Control Studies, Human genome, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Large-scale DNA databanks linked to electronic medical record (EMR) systems have been proposed as an approach for rapidly generating large, diverse cohorts for discovery and replication of genotype-phenotype associations. However, the extent to which such resources are capable of delivering on this promise is unknown. We studied whether an EMR-linked DNA biorepository can be used to detect known genotype-phenotype associations for five diseases. Twenty-one SNPs previously implicated as common variants predisposing to atrial fibrillation, Crohn disease, multiple sclerosis, rheumatoid arthritis, or type 2 diabetes were successfully genotyped in 9483 samples accrued over 4 mo into BioVU, the Vanderbilt University Medical Center DNA biobank. Previously reported odds ratios (OR(PR)) ranged from 1.14 to 2.36. For each phenotype, natural language processing techniques and billing-code queries were used to identify cases (n = 70-698) and controls (n = 808-3818) from deidentified health records. Each of the 21 tests of association yielded point estimates in the expected direction. Previous genotype-phenotype associations were replicated (p0.05) in 8/14 cases when the OR(PR) was1.25, and in 0/7 with lower OR(PR). Statistically significant associations were detected in all analyses that were adequately powered. In each of the five diseases studied, at least one previously reported association was replicated. These data demonstrate that phenotypes representing clinical diagnoses can be extracted from EMR systems, and they support the use of DNA resources coupled to EMR systems as tools for rapid generation of large data sets required for replication of associations found in research cohorts and for discovery in genome science.

Published
2010

21. Toxicology and Genetics of Adverse Drug Events

Author

Dan M. Roden

Subjects
Drug, Toxicology, Gene by environment, Drug Prescribing, Adverse drug event, Drug elimination, business.industry, media_common.quotation_subject, Medicine, Medical prescription, business, media_common
Abstract

Publisher Summary In this chapter, the term “adverse drug event” (ADE), rather than “reaction,” is used to emphasize that these occurrences are usually multifactorial and often include both biologic and system issues. No drug is free of ADE risk, and prescription of a drug therefore requires that the physician estimate that the risks of therapy are outweighed by the benefits. The list of ADEs for any given drug, let alone for all drugs commonly used by one practitioner, is enormous, and so the problem of ADEs presents challenges not only in guiding prescriptions to maximize benefit and minimize risk, but also in educating health practitioners in making such judgments in an increasingly complex molecular and genetic environment. Clearly, information tools play an increasing role in future drug prescribing. The chapter briefly explains the types of adverse drug events such as system errors, linking events to drug administration—the “easy” examples, linking events to drug administration—the “hard” examples, and many more. Furthermore, it also explains drug interactions that are especially likely to cause ADEs because they inhibit specific pathways for drug elimination. In this situation, ADEs are likely if a second “high-risk” drug using that pathway is also administered.

Published
2009
Full Text
View/download PDF

22. Contributors

Author

John C. Alexander, Donna K. Arnett, James R. Baker, Stacey L. Berg, Gordon R. Bernard, Italo Biaggioni, Robert A. Branch, Nancy J. Brown, Shama Buch, Robert M. Califf, Henry C. Chueh, Steven A. Claas, Christopher Clark, Christopher H. Colecchi, Robert J. Creeden, William F. Crowley, Joann L. Data, Zeruesenay Desta, Trung Q. Do, Sukru Mehmet Erturk, Luigi Ferrucci, David A. Flockhart, Catharyn Gildesgame, Steven Grinspoon, Katherine E. Hartmann, Elizabeth Heitman, Brian N. Hicks, Marc Hurlbert, Ciaran Johnston, Hylton V. Joffe, Quarraisha Abdool Karim, Richard B. Kim, Roger Kitterman, Bruce R. Korf, Greg Koski, Ronald L. Krall, Nancy Lugn, Joseph Massaro, Ginger L. Milne, Gary F. Mitchell, Jason D. Morrow, Shawn N. Murphy, Kenneth T. Norris, Mary H. Parks, Uwe E. Reinhardt, Neil M. Resnick, Todd W. Rice, David Robertson, Dan M. Roden, Angela J. Rogers, Daniel E. Salazar, Achara Sathienkijkanchai, Alan F. Schatzberg, J. Sanford Schwartz, Ellen W. Seely, Donald C. Simonson, Ann R. Stark, Stephanie Studenski, Nancy S. Sung, Clare Tempany-Afdhal, Marcia A. Testa, Thommey P. Thomas, Rommel G. Tirona, Frances Toneguzzo, Annick D. Van den Abbeele, Sten H. Vermund, Brent B. Ward, Scott Weiss, Gordon H. Williams, Mary Woolley, Nikki Zapol, Scott L. Zeger, and Nathalie Zgheib

Published
2009
Full Text
View/download PDF

23. CONTRIBUTORS

Author

Darrell R. Abernethy, Viola Andresen, Arthur J. Atkinson, Michel Azizi, Helen L. Baron, Carol L. Beck, Atta Behfar, Rodney Bell, Eduardo E. Benarroch, Neal L. Benowitz, Wade Berrettini, Joseph S. Bertino, Alfredo Bianchi, Michael J. Blake, Ann F. Bolger, Glenn D. Braunstein, David Brock, Peter A. Calabresi, Michael Camilleri, Mark Chaballa, Omer Chaudhry, Doo-Sup Choi, Bart L. Clarke, Mary E. Dankert, Dawood Darbar, Mark Davis, Daniel Deck, Jan de Gans, Joseph A. DeSimone, Robert B. Diasio, André Diedrich, Darin D. Dougherty, Laurence J. Egan, Claudine El-Beyrouty, Jean-Luc Elghozi, Arthur M. Feldman, Joanne Filicko-O'Hara, Charles W. Flexner, Neal Flomenberg, Joseph F. Foss, Adam M. Frank, Mark A. Frye, Kishor Gandhi, Joseph Genebriera, William R. Gilliland, Jean Gray, Benjamin M. Greenberg, Naomi Gronich, Dolores Grosso, Andrew R. Haas, Wael N. Haidar, Christine A. Haller, Daniel K. Hall-Flavin, Lisa Hamaker, William F. Harvey, James W. Heitz, Steven K. Herrine, Raymond J. Hohl, Sarah A. Holstein, Dorothy Holt, Linda S. Hostelley, Eric R. Houpt, Shiew-Mei Huang, David J. Hunter, Serge Jabbour, Robert M. Jacobson, Arshad Jahangir, Michael A. Jenike, Kristine E. Johnson, Victor M. Karpyak, Gregory L. Kearns, Richard M. Keating, Michael P. Keith, Sundeep Khosla, Julia Kirchheiner, Walter J. Koch, Bruce C. Kone, Walter K. Kraft, Robert F. Kushner, Christine Laine, Richard L. Lalonde, Kiwon Lee, Teofilo Lee-Chiong, Frank T. Leone, Lawrence J. Lesko, Barbara A. Levey, Lionel D. Lewis, Joseph Loscalzo, Anastasios Lymperopoulos, Joseph P. Lynch, Christian Maaser, Viqar Maria, Paul E. Marik, Marco A. Maurtua, Steven E. McKenzie, Alex Mejia, Michael C. Milone, Scott Mintzer, Thomas P. Moyer, David A. Mrazek, Matthew S. Murphy, Filip Mussen, Jasmine Nabi, Victor J. Navarro, Timothy J. Nelson, Dionissios Neofytos, Kathleen A. Neville, Myaing Nyunt, Timothy O'Brien, Inna G. Ovsyannikova, Chi-Un Pae, James F. Pagel, Ashwin A. Patkar, Kah Whye Peng, Edith A. Perez, Ronald C. Petersen, Paul A. Pham, Jennifer M. Phillips, Carissa Pineda, Mark R. Pittelkow, Pierre-François Plouin, Christopher V. Plowe, Gregory A. Poland, Azad Raiesdana, John N. Ratchford, Nandi J. Reddy, Michael D. Reed, Douglas J. Rhee, Robert A. Rizza, David Robertson, Dan M. Roden, Anne M. Rompalo, Simona Rossi, Vivek Roy, Stephen J. Russell, Steven Ryder, Muhammad Wasif Saif, Rajiv Saini, Kyoko Sato, Kathryn M. Schak, Matthias Schwab, Kumar Sharma, Robert G. Sharrar, Leslie M. Shaw, Ludy Shih, Steven J. Siegel, Peter A. Singer, David R. Staskin, Dale W. Stovall, Jerome F. Strauss, Paul V. Targonski, Daniel Tarsy, William S. Tasman, Robert Temple, Andre Terzic, John E. Tetzlaff, Pritish K. Tosh, Erev E. Tubb, Kathleen Uhl, Patrick Vallance, Diederik van de Beek, Adrian Vella, Eugene R. Viscusi, John L. Wagner, Scott A. Waldman, Philip B. Wedegaertner, Alan J. Wein, Ethan Weiner, Richard Weinshilboum, Martijn Weisfelt, Lisa G. Winston, Run Yu, and Ying Zhang

Published
2009
Full Text
View/download PDF

26. Pharmacogenomics of Cardiac Arrhythmias and Impact on Drug Therapy

Author

Dan M. Roden

Subjects
Drug, business.industry, media_common.quotation_subject, Drug action, Pharmacology, Pharmacotherapy, Pharmacokinetics, Pharmacodynamics, Pharmacogenomics, Molecular targets, Medicine, business, Molecular site, media_common
Abstract

Individuals vary widely in their responses to therapy with most drugs. Indeed, responses to antiarrhythmic drug therapy are so highly variable that study of the underlying mechanisms has elucidated important lessons for understanding variable responses to drug therapy in general. There are two key steps in the long series of events that take place between administration of a drug and manifestation of its effects. First, the drug must enter the systemic circulation and access its molecular site of action (receptor, ion channel, etc.). The magnitude of the effect at the target is determined by drug concentration, and the study of the relationship of drug dose and concentration of drug (and metabolites) achieved in plasma, tissue, or other sites such as urine or bile is termed pharmacokinetics . The second major process that determines drug action has been termed pharmacodynamics and refers broadly to the processes that must occur between a drug interacting with a specific molecular target and manifestation of drug action at the molecular, cellular, whole organ, and whole patient levels. Because drugs act in a complex (and often abnormal) biologic milieu, considerable intersubject variability in drug effects may arise from pharmacodynamic mechanisms.

Published
2004
Full Text
View/download PDF

27. The Autonomic Nervous System and Sudden Cardiac Death

Author

Dan M. Roden

Subjects
medicine.medical_specialty, Heart disease, business.industry, Baroreflex, medicine.disease, Sudden death, Sudden cardiac death, Autonomic nervous system, Heart failure, Internal medicine, medicine, Cardiology, Heart rate variability, Myocardial infarction, Intensive care medicine, business
Abstract

Publisher Summary This chapter highlights the influence of the autonomic nervous system (ANS) in the sudden cardiac death (SCD). The problem of sudden death remains a huge public health issue. It is clear that there is a prominent autonomic influence on risk. Evidence from clinical studies points to a prominent role of autonomic activation in SCD. In the late 1970s, landmark clinical trials established that β-blocker therapy in patients surviving acute myocardial infarction was highly effective in reducing overall mortality and SCD, and this has now become the standard of care. Markers of activation of the ANS—such as increased plasma norepinephrine (NE)—have been shown to be sensitive markers of mortality in patients with heart failure from all causes, and judicious use of β-blockers has shown to reduce mortality in this setting as well. Markers of autonomic dysfunction in patients with heart disease include reduced heart rate variability and blunted baroreflex sensitiv. Studies in humans and in cellular and animal models are currently elucidating molecular and genetic mechanisms modulating that risk. The development of improved therapies, possibly by modulating specifically targeted intracellular signaling pathways, may result in reduced risk for this devastating health issue.

Published
2004
Full Text
View/download PDF

28. Contributors

Author

MICHAEL J. ACKERMAN, FELIPE AGUEL, CESAR ALBERTE-LISTA, MATTHIAS ANTZ, CHARLES ANTZELEVITCH, JUSTUS M.B. ANUMONWO, RISHI ARORA, PETER H. BACKX, JEFFREY R. BALSER, KAREN BECKMAN, DAVID G. BENDITT, EDWARD J. BERBARI, OMER BERENFELD, DONALD M. BERS, ERIC C. BEYER, MARTIN BIEL, NEIL E. BOWLES, MARK R. BOYETT, JOSEP BRUGADA, PEDRO BRUGADA, RAMON BRUGADA, NENAD BURSAC, ALFRED E. BUXTON, MICHAEL E. CAIN, HUGH CALKINS, DAVID J. CALLANS, RICCARDO CAPPATO, SHEILA J. CARROLL, AGUSTIN CASTELLANOS, LAN S. CHEN, PENG-SHENG CHEN, SHIN-ANN CHEN, XIONGWEN CHEN, DAVID E. CLAPHAM, JACQUES CLÉMENTY, HARRY J. CRIJNS, EMILE G. DAOUD, MITHILESH K. DAS, MARIO DELMAR, DARIO DIFRANCESCO, JOHN P. DIMARCO, HALINA DOBRZYNSKI, HEATHER S. DUFFY, IGOR R. EFIMOV, JOACHIM R. EHRLICH, NABIL EL-SHERIF, KENNETH A. ELLENBOGEN, ANDREW E. EPSTEIN, CENGIZ ERMIS, SABINE ERNST, N. A. MARK ESTES, VLADIMIR G. FAST, VADIM V. FEDOROV, GUY FONTAINE, SARA FORESTI, PAUL FORNES, ROBERT FRANK, MICHAEL R. FRANZ, JOSEPH M. GALVIN, ALAN GARFINKEL, ANNE M. GILLIS, MICHAEL R. GOLD, JEFFREY GOLDBERGER, RICHARD A. GRAY, WOLFRAM GRIMM, WILLIAM J. GROH, DAVID E. HAINES, MICHEL HAÏSSAGUERRE, CARLOS HARO, DAVID L. HAYES, VOLODYA HAYRAPETYAN, JEAN-LOUIS HEBERT, CRAIG S. HENRIQUEZ, STEFAN HERRMANN, GERHARD HINDRICKS, MÉLÈZE HOCINI, FRANZ HOFMANN, STEFAN H. HOHNLOSER, HARUO HONJO, STEVEN R. HOUSER, LARRY V. HRYSHKO, EDWARD W. HSU, JIAN HUANG, JEAN-SÉBASTIEN HULOT, GARY D. HUTCHINS, RAYMOND E. IDEKER, ALBERTO INTERIAN, SEI IWAI, WARREN M. JACKMAN, PIERRE JAÏS, JOSÉ JALIFE, CRAIG T. JANUARY, CHRISTOPHER R. JOHNSON, MARK E. JOSEPHSON, XAVIER JOUVEN, ALAN H. KADISH, JONATHAN M. KALMAN, TIMOTHY J. KAMP, ROBERT S. KASS, HAROLD L. KENNEDY, RICHARD E. KERBER, ANANT KHOSITSETH, MICHAEL J. KILBORN, ANDRÉ G. KLÉBER, GEORGE J. KLEIN, BRADLEY P. KNIGHT, ITSUO KODAMA, HANS KOTTKAMP, ANDREW D. KRAHN, JAN P. KUCERA, KARL-HEINZ KUCK, JOHN D. KUGLER, CHI TAI KUO, JUNKO KUROKAWA, MAX J. LAB, WEN TER LAI, CLAIRE LARSON, KENNETH R. LAURITA, RALPH LAZZARA, BRUCE B. LERMAN, DEBORAH L. LERNER, SAMUEL LÉVY, RONALD A. LI, DAVID LIN, DEBORAH LOCKWOOD, BARRY LONDON, FEI LÜ, ANDREAS LUDWIG, JONATHAN C. MAKIELSKI, MAREK MALIK, EDUARDO MARBÁN, FRANCIS E. MARCHLINSKI, VIAS MARKIDES, STEVEN M. MARKOWITZ, BARRY J. MARON, AGUSTÍN D. MARTÍNEZ, MARK A. MCGUIRE, GERHARD MEISSNER, WILLIAM M. MILES, JOHN M. MILLER, MICHAEL A. MILLER, SUNEET MITTAL, FEDERICO MOLEIRO, SVEN MOOSMANG, FRED MORADY, ALONSO P. MORENO, ARTHUR J. MOSS, ROBERT J. MYERBURG, HIROSHI NAKAGAWA, CARLO NAPOLITANO, STANLEY NATTEL, JEANNE M. NERBONNE, VLADIMIR P. NIKOLSKI, JEFFREY E. OLGIN, HAKAN ORAL, KENICHIRO OTOMO, GAVIN Y. OUDIT, FEIFAN OUYANG, PIERRE L. PAGÉ, CARLO PAPPONE, EUGENE PATTERSON, ARKADY M. PERTSOV, NICHOLAS S. PETERS, ROBERT W. PETERS, SILVIA G. PRIORI, CATHERINE PROST-SQUARCIONI, ERIC N. PRYSTOWSKI, BONNIE B. PUNSKE, ZHILIN QU, RAFAEL J. RAMIREZ, ILARIA RIVOLTA, RICHARD B. ROBINSON, DAN M. RODEN, STEPHAN ROHR, SALVATORE ROSANIO, MICHAEL R. ROSEN, DAVID S. ROSENBAUM, LEONID V. ROSENSHTRAUKH, BRADLEY J. ROTH, YORAM RUDY, JEREMY N. RUSKIN, FREDERICK SACHS, JEFFREY E. SAFFITZ, PRASHANTHAN SANDERS, MICHAEL C. SANGUINETTI, NADIR SAOUDI, BENJAMIN J. SCHERLAG, PETER J. SCHWARTZ, DAVID SCHWARTZMAN, OLIVER R. SEGAL, DIPEN C. SHAH, OLEG F. SHARIFOV, KALYANAM SHIVKUMAR, JEFFREY SIMMONS, BRAMAH N. SINGH, ALLAN C. SKANES, TIMOTHY W. SMITH, KYOKO SOEJIMA, PAUL L. SORGEN, DAVID C. SPRAY, MIDUTURU SRINIVAS, KENNETH M. STEIN, SUSAN F. STEINBERG, WILLIAM G. STEVENSON, JULIANE STIEBER, MARCO STRAMBA-BADIALE, S. ADAM STRICKBERGER, RUEY J. SUNG, MICHAEL O. SWEENEY, CHARLES D. SWERDLOW, BRUNO TACCARDI, STEVEN M. TAFFET, CHING-TAI TAI, DANIEL THOMAS, GORDON F. TOMASELLI, FERNANDO TONDATO, JEFFREY A. TOWBIN, JOSEPH V. TRANQUILLO, NATALIA A. TRAYANOVA, JOHN K. TRIEDMAN, MARTIN TRISTANI-FIROUZI, CHIN-FENG TSAI, LESLIE TUNG, GIOIA TURITTO, GEORGE F. VAN HARE, DAVID R. VAN WAGONER, MARC A. VOS, GREGORY P. WALCOTT, ALBERT L. WALDO, ZULU WANG, KENNETH M. WEINBERG, DAVID WEINSTEIN, MARCEL WELLNER, BRUCE L. WILKOFF, MARK A. WOOD, JIANYI WU, JIASHIN WU, D. GEORGE WYSE, KATHRYN A. YAMADA, BIN YE, RAYMOND YEE, ALEXEY V. ZAITSEV, WOJCIECH ZAREBA, GUOQIANG ZHONG, and DOUGLAS P. ZIPES

Published
2004
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results