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1. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author

Bihlmeyer, Nathan A, Brody, Jennifer A, Smith, Albert Vernon, Warren, Helen R, Lin, Honghuang, Isaacs, Aaron, Liu, Ching-Ti, Marten, Jonathan, Radmanesh, Farid, Hall, Leanne M, Grarup, Niels, Mei, Hao, Müller-Nurasyid, Martina, Huffman, Jennifer E, Verweij, Niek, Guo, Xiuqing, Yao, Jie, Li-Gao, Ruifang, van den Berg, Marten, Weiss, Stefan, Prins, Bram P, van Setten, Jessica, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Li, Man, Alonso, Alvaro, Soliman, Elsayed Z, Bis, Joshua C, Austin, Tom, Chen, Yii-Der Ida, Psaty, Bruce M, Harrris, Tamara B, Launer, Lenore J, Padmanabhan, Sandosh, Dominiczak, Anna, Huang, Paul L, Xie, Zhijun, Ellinor, Patrick T, Kors, Jan A, Campbell, Archie, Murray, Alison D, Nelson, Christopher P, Tobin, Martin D, Bork-Jensen, Jette, Hansen, Torben, Pedersen, Oluf, Linneberg, Allan, Sinner, Moritz F, Peters, Annette, Waldenberger, Melanie, Meitinger, Thomas, Perz, Siegfried, Kolcic, Ivana, Rudan, Igor, de Boer, Rudolf A, van der Meer, Peter, Lin, Henry J, Taylor, Kent D, de Mutsert, Renée, Trompet, Stella, Jukema, J Wouter, Maan, Arie C, Stricker, Bruno HC, Rivadeneira, Fernando, Uitterlinden, André, Völker, Uwe, Homuth, Georg, Völzke, Henry, Felix, Stephan B, Mangino, Massimo, Spector, Timothy D, Bots, Michiel L, Perez, Marco, Raitakari, Olli T, Kähönen, Mika, Mononen, Nina, Gudnason, Vilmundur, Munroe, Patricia B, Lubitz, Steven A, van Duijn, Cornelia M, Newton-Cheh, Christopher H, Hayward, Caroline, Rosand, Jonathan, Samani, Nilesh J, Kanters, Jørgen K, Wilson, James G, Kääb, Stefan, Polasek, Ozren, van der Harst, Pim, Heckbert, Susan R, Rotter, Jerome I, Mook-Kanamori, Dennis O, Eijgelsheim, Mark, Dörr, Marcus, Jamshidi, Yalda, Asselbergs, Folkert W, Kooperberg, Charles, Lehtimäki, Terho, Arking, Dan E, and Sotoodehnia, Nona

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Prevention, Genetics, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Antiporters, DNA-Binding Proteins, Electrocardiography, Exome, Genome-Wide Association Study, Humans, Long QT Syndrome, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptors, Calcium-Sensing, Transcription Factors, arrhythmias, cardiac, death, sudden, cardiac, genetics, genome, humans, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundQT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.Methods and resultsWe performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci.ConclusionsOur analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.

Published
2018

2. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Author

Nolte, Ilja, Munoz, M, Tragante, Vinicius, Amare, Azmeraw, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy, Bis, Joshua, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen, Kluttig, Alexander, Krijthe, Bouwe, Kumar, Jitender, van der Laan, Sander, Lyytikäinen, Leo-Pekka, Maihofer, Adam, Minassian, Arpi, van der Most, Peter, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James, Thayer, Julian, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen, de Bakker, Paul, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George, Ellinor, Patrick, Eskola, Markku, Felix, Janine, Floras, John, Franco, Oscar, Friberg, Peter, Gademan, Maaike, Geyer, Mark, Giedraitis, Vilmantas, Hartman, Catharina, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti, Kors, Jan, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy, Lefrandt, Joop, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian, Lin, Henry, Lindgren, Cecilia, Lubitz, Steven, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew, Nalls, Mike, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari, OConnor, Daniel, Ormel, Johan, Perz, Siegfried, Peters, Annette, and Psaty, Bruce

Abstract

This corrects the article DOI: 10.1038/ncomms15805.

Published
2017

3. Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Author

Nolte, Ilja M, Munoz, M Loretto, Tragante, Vinicius, Amare, Azmeraw T, Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L, Bis, Joshua C, Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M, Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F, Kluttig, Alexander, Krijthe, Bouwe P, Kumar, Jitender, van der Laan, Sander W, Lyytikäinen, Leo-Pekka, Maihofer, Adam X, Minassian, Arpi, van der Most, Peter J, Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D, Thayer, Julian F, Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H, Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G, de Bakker, Paul IW, Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J, Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R, Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B, Ellinor, Patrick T, Eskola, Markku, Felix, Janine F, Floras, John S, Franco, Oscar H, Friberg, Peter, Gademan, Maaike GJ, Geyer, Mark A, Giedraitis, Vilmantas, Hartman, Catharina A, Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M, Kors, Jan A, Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C, Lefrandt, Joop D, Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C, Lin, Henry J, Lindgren, Cecilia M, Lubitz, Steven A, Mahajan, Anubha, McKnight, Barbara, Zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P, Nalls, Mike A, Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E, O'Connor, Daniel T, Ormel, Johan, Perz, Siegfried, Peters, Annette, and Psaty, Bruce M

Subjects
Humans, Heart Diseases, Genetic Predisposition to Disease, RGS Proteins, Potassium Channels, Muscle Proteins, Risk Factors, Cohort Studies, Blood Pressure, Heart Rate, Polymorphism, Single Nucleotide, Quantitative Trait Loci, European Continental Ancestry Group, Genome-Wide Association Study, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Cardiovascular, Genetics, Heart Disease
Abstract

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g

Published
2017

4. 52 Genetic Loci Influencing Myocardial Mass

Author

van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Leach, Irene Mateo, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M., Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, and Schmidt, Carsten O

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Genetics, Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, Biotechnology, Human Genome, 2.1 Biological and endogenous factors, Animals, Cardiomegaly, Genetic Loci, Genome-Wide Association Study, Humans, electrocardiogram, genetic association study, heart failure, left ventricular hypertrophy, QRS, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundMyocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.ObjectivesThis meta-analysis sought to gain insights into the genetic determinants of myocardial mass.MethodsWe carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.ResultsWe identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.ConclusionsTaken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.

Published
2016

5. Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction

Author

Sotoodehnia, Nona, Isaacs, Aaron, de Bakker, Paul IW, Dörr, Marcus, Newton-Cheh, Christopher, Nolte, Ilja M, van der Harst, Pim, Müller, Martina, Eijgelsheim, Mark, Alonso, Alvaro, Hicks, Andrew A, Padmanabhan, Sandosh, Hayward, Caroline, Smith, Albert Vernon, Polasek, Ozren, Giovannone, Steven, Fu, Jingyuan, Magnani, Jared W, Marciante, Kristin D, Pfeufer, Arne, Gharib, Sina A, Teumer, Alexander, Li, Man, Bis, Joshua C, Rivadeneira, Fernando, Aspelund, Thor, Köttgen, Anna, Johnson, Toby, Rice, Kenneth, Sie, Mark PS, Wang, Ying A, Klopp, Norman, Fuchsberger, Christian, Wild, Sarah H, Leach, Irene Mateo, Estrada, Karol, Völker, Uwe, Wright, Alan F, Asselbergs, Folkert W, Qu, Jiaxiang, Chakravarti, Aravinda, Sinner, Moritz F, Kors, Jan A, Petersmann, Astrid, Harris, Tamara B, Soliman, Elsayed Z, Munroe, Patricia B, Psaty, Bruce M, Oostra, Ben A, Cupples, L Adrienne, Perz, Siegfried, de Boer, Rudolf A, Uitterlinden, André G, Völzke, Henry, Spector, Timothy D, Liu, Fang-Yu, Boerwinkle, Eric, Dominiczak, Anna F, Rotter, Jerome I, van Herpen, Gé, Levy, Daniel, Wichmann, H-Erich, van Gilst, Wiek H, Witteman, Jacqueline CM, Kroemer, Heyo K, Kao, WH Linda, Heckbert, Susan R, Meitinger, Thomas, Hofman, Albert, Campbell, Harry, Folsom, Aaron R, van Veldhuisen, Dirk J, Schwienbacher, Christine, O'Donnell, Christopher J, Volpato, Claudia Beu, Caulfield, Mark J, Connell, John M, Launer, Lenore, Lu, Xiaowen, Franke, Lude, Fehrmann, Rudolf SN, te Meerman, Gerard, Groen, Harry JM, Weersma, Rinse K, van den Berg, Leonard H, Wijmenga, Cisca, Ophoff, Roel A, Navis, Gerjan, Rudan, Igor, Snieder, Harold, Wilson, James F, Pramstaller, Peter P, Siscovick, David S, Wang, Thomas J, Gudnason, Vilmundur, van Duijn, Cornelia M, Felix, Stephan B, Fishman, Glenn I, Jamshidi, Yalda, and Ch Stricker, Bruno H

Subjects
Biological Sciences, Genetics, Cardiovascular, Heart Disease, Animals, Animals, Newborn, Chromosomes, Human, Computational Biology, Electrocardiography, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Humans, Mice, Mice, Transgenic, Models, Animal, Myocytes, Cardiac, NAV1.8 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Sodium Channels, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

Published
2010

6. Associations between calcium and vitamin D supplement use as well as their serum concentrations and subclinical cardiovascular disease phenotypes

Author

Thiele, Inke, Linseisen, Jakob, Meisinger, Christa, Schwab, Sigrid, Huth, Cornelia, Peters, Annette, Perz, Siegfried, Meitinger, Thomas, Kronenberg, Florian, Lamina, Claudia, Thiery, Joachim, Koenig, Wolfgang, Rathmann, Wolfgang, Kääb, Stefan, Then, Cornelia, Seissler, Jochen, and Thorand, Barbara

Published
2015
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8. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author

Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikäinen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Müller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kähönen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundström, Johan, Swenne, Cees A., Syvänen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, André G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B, Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Järvelin, Marjo-Riitta, Kääb, Stefan, Kähönen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimäki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriëtte, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J.M, Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, and de Geus, Eco J. C.

Published
2017
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12. Genome-wide association analysis identifies multiple loci related to resting heart rate

Author

Eijgelsheim, Mark, Newton-Cheh, Christopher, Sotoodehnia, Nona, de Bakker, Paul I.W., Müller, Martina, Morrison, Alanna C., Smith, Albert V., Isaacs, Aaron, Sanna, Serena, Dörr, Marcus, Navarro, Pau, Fuchsberger, Christian, Nolte, Ilja M., de Geus, Eco J.C., Estrada, Karol, Hwang, Shih-Jen, Bis, Joshua C., Rückert, Ina-Maria, Alonso, Alvaro, Launer, Lenore J., Hottenga, Jouke Jan, Rivadeneira, Fernando, Noseworthy, Peter A., Rice, Kenneth M., Perz, Siegfried, Arking, Dan E., Spector, Tim D., Kors, Jan A., Aulchenko, Yurii S., Tarasov, Kirill V., Homuth, Georg, Wild, Sarah H., Marroni, Fabio, Gieger, Christian, Licht, Carmilla M., Prineas, Ronald J., Hofman, Albert, Rotter, Jerome I., Hicks, Andrew A., Ernst, Florian, Najjar, Samer S., Wright, Alan F., Peters, Annette, Fox, Ervin R., Oostra, Ben A., Kroemer, Heyo K., Couper, David, Völzke, Henry, Campbell, Harry, Meitinger, Thomas, Uda, Manuela, Witteman, Jacqueline C.M., Psaty, Bruce M., Wichmann, H-Erich, Harris, Tamara B., Kääb, Stefan, Siscovick, David S., Jamshidi, Yalda, Uitterlinden, André G., Folsom, Aaron R., Larson, Martin G., Wilson, James F., Penninx, Brenda W., Snieder, Harold, Pramstaller, Peter P., van Duijn, Cornelia M., Lakatta, Edward G., Felix, Stephan B., Gudnason, Vilmundur, Pfeufer, Arne, Heckbert, Susan R., Stricker, Bruno H.Ch., Boerwinkle, Eric, and OʼDonnell, Christopher J.

Published
2010
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14. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation

Author

Kääb, Stefan, Darbar, Dawood, van Noord, Charlotte, Dupuis, Josée, Pfeufer, Arne, Newton-Cheh, Christopher, Schnabel, Renate, Makino, Seiko, Sinner, Moritz F., Kannankeril, Prince J., Beckmann, Britt M., Choudry, Subbarao, Donahue, Brian S., Heeringa, Jan, Perz, Siegfried, Lunetta, Kathryn L., Larson, Martin G., Levy, Daniel, MacRae, Calum A., Ruskin, Jeremy N., Wacker, Annette, Schömig, Albert, Wichmann, H-Erich, Steinbeck, Gerhard, Meitinger, Thomas, Uitterlinden, André G., Witteman, Jacqueline C.M., Roden, Dan M., Benjamin, Emelia J., and Ellinor, Patrick T.

Published
2009

19. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Author

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

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

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

Published
2018

20. Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy

Author

Schunkert, Heribert, Hense, Hans-Werner, Holmer, Stephan R., Stender, Monica, Perz, Siegfried, Keil, Ulrich, Lorell, Beverly H., and Riegger, Gunter A.J.

Subjects
Chromosome deletion -- Health aspects, Genetic polymorphisms -- Health aspects, Heart enlargement -- Genetic aspects, Angiotensin converting enzyme -- Genetic aspects
Abstract

Left ventricular hypertrophy (LVH) (enlargement of the heart) may be related to genetic background. Specifically, it may be related to a deletion-insertion polymorphism of the angiotensin-converting-enzyme (ACE) gene. Other factors that may influence left ventricular hypertrophy are absence of an elevated cardiac workload, obesity, hemodynamic overload, and environmental factors. LVH is a risk factor for cardiovascular disease. Electrocardiography was used to identify and measure LVH in 290 of 1,428 German patients studied. Men who were homozygous for the ACE genotype, or who had two identical alleles (alternative form of a gene) at one locus (position of a gene on a chromosome), had a 2.63 greater occurrence of LVH than other men. Sixty-two percent of subjects with LVH did not have hypertension, weakening any correlation between the two.

Published
1994

22. Erratum: Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Author

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

Published
2017

23. Genetic loci associated with heart rate variability and their effects on cardiac disease risk (vol 8, pg 15805, 2017)

Author

Nolte, Ilja M., Munoz, M. Loretto, Tragante, Vinicius, Amare, Azmeraw T., Jansen, Rick, Vaez, Ahmad, von der Heyde, Benedikt, Avery, Christy L., Bis, Joshua C., Dierckx, Bram, van Dongen, Jenny, Gogarten, Stephanie M., Goyette, Philippe, Hernesniemi, Jussi, Huikari, Ville, Hwang, Shih-Jen, Jaju, Deepali, Kerr, Kathleen F., Kluttig, Alexander, Krijthe, Bouwe P., Kumar, Jitender, van der Laan, Sander W., Lyytikainen, Leo-Pekka, Maihofer, Adam X., Minassian, Arpi, van der Most, Peter J., Mueller-Nurasyid, Martina, Nivard, Michel, Salvi, Erika, Stewart, James D., Thayer, Julian F., Verweij, Niek, Wong, Andrew, Zabaneh, Delilah, Zafarmand, Mohammad H., Abdellaoui, Abdel, Albarwani, Sulayma, Albert, Christine, Alonso, Alvaro, Ashar, Foram, Auvinen, Juha, Axelsson, Tomas, Baker, Dewleen G., de Bakker, Paul I. W., Barcella, Matteo, Bayoumi, Riad, Bieringa, Rob J., Boomsma, Dorret, Boucher, Gabrielle, Britton, Annie R., Christophersen, Ingrid, Dietrich, Andrea, Ehret, George B., Ellinor, Patrick T., Eskola, Markku, Felix, Janine F., Floras, John S., Franco, Oscar H., Friberg, Peter, Gademan, Maaike G. J., Geyer, Mark A., Giedraitis, Vilmantas, Hartman, Catharina A., Hemerich, Daiane, Hofman, Albert, Hottenga, Jouke-Jan, Huikuri, Heikki, Hutri-Kahonen, Nina, Jouven, Xavier, Junttila, Juhani, Juonala, Markus, Kiviniemi, Antti M., Kors, Jan A., Kumari, Meena, Kuznetsova, Tatiana, Laurie, Cathy C., Lefrandt, Joop D., Li, Yong, Li, Yun, Liao, Duanping, Limacher, Marian C., Lin, Henry J., Lindgren, Cecilia M., Lubitz, Steven A., Mahajan, Anubha, McKnight, Barbara, zu Schwabedissen, Henriette Meyer, Milaneschi, Yuri, Mononen, Nina, Morris, Andrew P., Nalls, Mike A., Navis, Gerjan, Neijts, Melanie, Nikus, Kjell, North, Kari E., O'Connor, Daniel T., Ormel, Johan, Perz, Siegfried, Peters, Annette, Psaty, Bruce M., Raitakari, Olli T., Risbrough, Victoria B., Sinner, Moritz F., Siscovick, David, Smit, Johannes H., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Staessen, Jan A., Stein, Phyllis K., Stilp, Adrienne M., Stolarz-Skrzypek, Katarzyna, Strauch, Konstantin, Sundstrom, Johan, Swenne, Cees A., Syvanen, Ann-Christine, Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thornton, Timothy A., Tinker, Lesley E., Uitterlinden, Andre G., van Setten, Jessica, Voss, Andreas, Waldenberger, Melanie, Wilhelmsen, Kirk C., Willemsen, Gonneke, Wong, Quenna, Zhang, Zhu-Ming, Zonderman, Alan B., Cusi, Daniele, Evans, Michele K., Greiser, Halina K., van der Harst, Pim, Hassan, Mohammad, Ingelsson, Erik, Jarvelin, Marjo-Riitta, Kaab, Stefan, Kahonen, Mika, Kivimaki, Mika, Kooperberg, Charles, Kuh, Diana, Lehtimaki, Terho, Lind, Lars, Nievergelt, Caroline M., O'Donnell, Chris J., Oldehinkel, Albertine J., Penninx, Brenda, Reiner, Alexander P., Riese, Harriette, van Roon, Arie M., Rioux, John D., Rotter, Jerome I., Sofer, Tamar, Stricker, Bruno H., Tiemeier, Henning, Vrijkotte, Tanja G. M., Asselbergs, Folkert W., Brundel, Bianca J. J. M., Heckbert, Susan R., Whitsel, Eric A., den Hoed, Marcel, Snieder, Harold, de Geus, Eco J. C., Biological Psychology, APH - Mental Health, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Faculty of Religion and Theology, and Environmental Geography (former)

Subjects
Netherlands Twin Register (NTR), Cardiovascular genetics Genome-wide association studies Risk factors
Abstract

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74

Published
2017
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24. Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

Author

Sinner, Moritz F., Reinhard, Wibke, Muller, Martina, Beckmann, Britt-Maria, Martens, Eimo, Perz, Siegfried, Pfeufer, Arne, Winogradow, Janina, Stark, Klaus, Meisinger, Christa, Wichmann, H.-Erich, Peters, Annette, Riegger, Gunter A.J., Steinbeck, Gerhard, Hengstenberg, Christian, and Kaab, Stefan

Subjects
Electrocardiography -- Analysis, Cardiovascular diseases -- Diagnosis -- Risk factors -- Patient outcomes, Electrocardiogram -- Analysis, Biological sciences
Abstract

Background: Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent. Methods and Findings: Electrocardiograms of 1,945 participants aged 35-74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9) codes as documented in death certificates. ERP- attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex;a clear ERP-age interaction was detected (p = 0.005). Age-stratified analyses showed hazard ratios (HRs) for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05-3.68, p = 0.035) for both sexes and 2.65 (95% CI 1.21-5.83, p = 0.015) for men between 35-54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58-6.28, p = 0.001) for both sexes and to 4.27 (95% CI 1.90-9.61, p Conclusions: We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior localization of ERP was associated with a particularly increased risk., Introduction The electrocardiographic pattern of early repolarization (ERP), a slurring or notching at the QRS-ST junction, is a common and long described finding on electrocardiogram (ECG) [1,2]. Its prevalence has [...]

Published
2010
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25. Session 6. Biosignal processing and monitoring I

Author

Schroeder, Rico, primary, Radon, Sarah, additional, Fischer, Claudia, additional, Valero, Mireia, additional, Vallverdu, Montserrat, additional, Peters, Annette, additional, Perz, Siegfried, additional, and Voss, Andreas, additional

Published
2017
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26. Are Electrocardiography Findings Associated with Disability in the Aged? Results from the KORA-Age study

Author

Röhrig, Nadine, Strobl, Ralf, Müller, Martin, Perz, Siegfried, Martens, Eimo, Kääb, Stefan, Linkohr, Birgit, Peters, Annette, and Grill, Eva

Subjects
aged, Disability, ddc: 610, ECG, DAG (Directed Acyclic Graph), cardiovascular diseases, 610 Medical sciences, Medicine
Abstract

Background: Cardiovascular disease (CVD) is among the leading chronic conditions that are associated with functional limitations and disability in the aged. There is increasing evidence that even subclinical diseases such as operationalized by electrocardiogram may substantially compromise functioning.[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)

Published
2011

28. A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern

Author

Sinner, Moritz F., primary, Porthan, Kimmo, additional, Noseworthy, Peter A., additional, Havulinna, Aki S., additional, Tikkanen, Jani T., additional, Müller-Nurasyid, Martina, additional, Peloso, Gina, additional, Ulivi, Sheila, additional, Beckmann, Britt Maria, additional, Brockhaus, A. Catharina, additional, Cooper, Rebecca R., additional, Gasparini, Paolo, additional, Hengstenberg, Christian, additional, Hwang, Shih-Jen, additional, Iorio, Annamaria, additional, Junttila, M. Juhani, additional, Klopp, Norman, additional, Kähönen, Mika, additional, Laaksonen, Maarit A., additional, Lehtimäki, Terho, additional, Lichtner, Peter, additional, Lyytikäinen, Leo-Pekka, additional, Martens, Eimo, additional, Meisinger, Christa, additional, Meitinger, Thomas, additional, Merchant, Faisal M., additional, Nieminen, Markku S., additional, Peters, Annette, additional, Pietilä, Arto, additional, Perz, Siegfried, additional, Oikarinen, Lasse, additional, Raitakari, Olli, additional, Reinhard, Wibke, additional, Silander, Kaisa, additional, Thorand, Barbara, additional, Wichmann, H.-Erich, additional, Sinagra, Gianfranco, additional, Viikari, Jorma, additional, O'Donnell, Christopher J., additional, Ellinor, Patrick T., additional, Huikuri, Heikki V., additional, Kääb, Stefan, additional, Newton-Cheh, Christopher, additional, and Salomaa, Veikko, additional

Published
2012
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29. Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Author

Ellinor, Patrick T, primary, Lunetta, Kathryn L, additional, Albert, Christine M, additional, Glazer, Nicole L, additional, Ritchie, Marylyn D, additional, Smith, Albert V, additional, Arking, Dan E, additional, Müller-Nurasyid, Martina, additional, Krijthe, Bouwe P, additional, Lubitz, Steven A, additional, Bis, Joshua C, additional, Chung, Mina K, additional, Dörr, Marcus, additional, Ozaki, Kouichi, additional, Roberts, Jason D, additional, Smith, J Gustav, additional, Pfeufer, Arne, additional, Sinner, Moritz F, additional, Lohman, Kurt, additional, Ding, Jingzhong, additional, Smith, Nicholas L, additional, Smith, Jonathan D, additional, Rienstra, Michiel, additional, Rice, Kenneth M, additional, Van Wagoner, David R, additional, Magnani, Jared W, additional, Wakili, Reza, additional, Clauss, Sebastian, additional, Rotter, Jerome I, additional, Steinbeck, Gerhard, additional, Launer, Lenore J, additional, Davies, Robert W, additional, Borkovich, Matthew, additional, Harris, Tamara B, additional, Lin, Honghuang, additional, Völker, Uwe, additional, Völzke, Henry, additional, Milan, David J, additional, Hofman, Albert, additional, Boerwinkle, Eric, additional, Chen, Lin Y, additional, Soliman, Elsayed Z, additional, Voight, Benjamin F, additional, Li, Guo, additional, Chakravarti, Aravinda, additional, Kubo, Michiaki, additional, Tedrow, Usha B, additional, Rose, Lynda M, additional, Ridker, Paul M, additional, Conen, David, additional, Tsunoda, Tatsuhiko, additional, Furukawa, Tetsushi, additional, Sotoodehnia, Nona, additional, Xu, Siyan, additional, Kamatani, Naoyuki, additional, Levy, Daniel, additional, Nakamura, Yusuke, additional, Parvez, Babar, additional, Mahida, Saagar, additional, Furie, Karen L, additional, Rosand, Jonathan, additional, Muhammad, Raafia, additional, Psaty, Bruce M, additional, Meitinger, Thomas, additional, Perz, Siegfried, additional, Wichmann, H-Erich, additional, Witteman, Jacqueline C M, additional, Kao, W H Linda, additional, Kathiresan, Sekar, additional, Roden, Dan M, additional, Uitterlinden, Andre G, additional, Rivadeneira, Fernando, additional, McKnight, Barbara, additional, Sjögren, Marketa, additional, Newman, Anne B, additional, Liu, Yongmei, additional, Gollob, Michael H, additional, Melander, Olle, additional, Tanaka, Toshihiro, additional, Stricker, Bruno H Ch, additional, Felix, Stephan B, additional, Alonso, Alvaro, additional, Darbar, Dawood, additional, Barnard, John, additional, Chasman, Daniel I, additional, Heckbert, Susan R, additional, Benjamin, Emelia J, additional, Gudnason, Vilmundur, additional, and Kääb, Stefan, additional

Published
2012
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30. A Large Candidate Gene Survey Identifies the KCNE1 D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes

Author

Kääb, Stefan, primary, Crawford, Dana C., additional, Sinner, Moritz F., additional, Behr, Elijah R., additional, Kannankeril, Prince J., additional, Wilde, Arthur A.M., additional, Bezzina, Connie R., additional, Schulze-Bahr, Eric, additional, Guicheney, Pascale, additional, Bishopric, Nanette H., additional, Myerburg, Robert J., additional, Schott, Jean-Jacques, additional, Pfeufer, Arne, additional, Beckmann, Britt-Maria, additional, Martens, Eimo, additional, Zhang, Taifang, additional, Stallmeyer, Birgit, additional, Zumhagen, Sven, additional, Denjoy, Isabelle, additional, Bardai, Abdennasser, additional, Van Gelder, Isabelle C., additional, Jamshidi, Yalda, additional, Dalageorgou, Chrysoula, additional, Marshall, Vanessa, additional, Jeffery, Steve, additional, Shakir, Saad, additional, Camm, A. John, additional, Steinbeck, Gerhard, additional, Perz, Siegfried, additional, Lichtner, Peter, additional, Meitinger, Thomas, additional, Peters, Annette, additional, Wichmann, H.-Erich, additional, Ingram, Christiana, additional, Bradford, Yuki, additional, Carter, Shannon, additional, Norris, Kris, additional, Ritchie, Marylyn D., additional, George, Alfred L., additional, and Roden, Dan M., additional

Published
2012
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31. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Author

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, 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, 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, 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, and Ellinor, Patrick T

Abstract

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. 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.

Published
2017
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32. Which QTc interval estimate is better for predicting sudden death?

Author

Perz, Siegfried, primary, Küfner, Roswitha, additional, Sinner, Moritz, additional, Meisinger, Christine, additional, Müller, Martina, additional, Pfeufer, Arne, additional, Peters, Annette, additional, Englmeier, Karl-Hans, additional, Wichmann, H.-Erich, additional, and Kääb, Stefan, additional

Published
2011
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33. Lack of replication in polymorphisms reported to be associated with atrial fibrillation

Author

Sinner, Moritz F., primary, Lubitz, Steven A., additional, Pfeufer, Arne, additional, Makino, Seiko, additional, Beckmann, Britt-Maria, additional, Lunetta, Kathryn L., additional, Steinbeck, Gerhard, additional, Perz, Siegfried, additional, Rahman, Rosanna, additional, Sonni, Akshata, additional, Greenberg, Steven M., additional, Furie, Karen L., additional, Wichmann, H.-Erich, additional, Meitinger, Thomas, additional, Peters, Annette, additional, Benjamin, Emelia J., additional, Rosand, Jonathan, additional, Ellinor, Patrick T., additional, and Kääb, Stefan, additional

Published
2011
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36. Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25

Author

Lubitz, Steven A., primary, Sinner, Moritz F., additional, Lunetta, Kathryn L., additional, Makino, Seiko, additional, Pfeufer, Arne, additional, Rahman, Rosanna, additional, Veltman, Caroline E., additional, Barnard, John, additional, Bis, Joshua C., additional, Danik, Stephan P., additional, Sonni, Akshata, additional, Shea, Marisa A., additional, del Monte, Federica, additional, Perz, Siegfried, additional, Müller, Martina, additional, Peters, Annette, additional, Greenberg, Steven M., additional, Furie, Karen L., additional, van Noord, Charlotte, additional, Boerwinkle, Eric, additional, Stricker, Bruno H.C., additional, Witteman, Jacqueline, additional, Smith, Jonathan D., additional, Chung, Mina K., additional, Heckbert, Susan R., additional, Benjamin, Emelia J., additional, Rosand, Jonathan, additional, Arking, Dan E., additional, Alonso, Alvaro, additional, Kääb, Stefan, additional, and Ellinor, Patrick T., additional

Published
2010
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37. Common variants in KCNN3 are associated with lone atrial fibrillation

Author

Ellinor, Patrick T, primary, Lunetta, Kathryn L, additional, Glazer, Nicole L, additional, Pfeufer, Arne, additional, Alonso, Alvaro, additional, Chung, Mina K, additional, Sinner, Moritz F, additional, de Bakker, Paul I W, additional, Mueller, Martina, additional, Lubitz, Steven A, additional, Fox, Ervin, additional, Darbar, Dawood, additional, Smith, Nicholas L, additional, Smith, Jonathan D, additional, Schnabel, Renate B, additional, Soliman, Elsayed Z, additional, Rice, Kenneth M, additional, Van Wagoner, David R, additional, Beckmann, Britt-M, additional, van Noord, Charlotte, additional, Wang, Ke, additional, Ehret, Georg B, additional, Rotter, Jerome I, additional, Hazen, Stanley L, additional, Steinbeck, Gerhard, additional, Smith, Albert V, additional, Launer, Lenore J, additional, Harris, Tamara B, additional, Makino, Seiko, additional, Nelis, Mari, additional, Milan, David J, additional, Perz, Siegfried, additional, Esko, Tõnu, additional, Köttgen, Anna, additional, Moebus, Susanne, additional, Newton-Cheh, Christopher, additional, Li, Man, additional, Möhlenkamp, Stefan, additional, Wang, Thomas J, additional, Linda Kao, W H, additional, Vasan, Ramachandran S, additional, Nöthen, Markus M, additional, MacRae, Calum A, additional, Ch Stricker, Bruno H, additional, Hofman, Albert, additional, Uitterlinden, André G, additional, Levy, Daniel, additional, Boerwinkle, Eric, additional, Metspalu, Andres, additional, Topol, Eric J, additional, Chakravarti, Aravinda, additional, Gudnason, Vilmundur, additional, Psaty, Bruce M, additional, Roden, Dan M, additional, Meitinger, Thomas, additional, Wichmann, H-Erich, additional, Witteman, Jacqueline C M, additional, Barnard, John, additional, Arking, Dan E, additional, Benjamin, Emelia J, additional, Heckbert, Susan R, additional, and Kääb, Stefan, additional

Published
2010
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38. Genome-wide association study of PR interval

Author

Pfeufer, Arne, primary, van Noord, Charlotte, additional, Marciante, Kristin D, additional, Arking, Dan E, additional, Larson, Martin G, additional, Smith, Albert Vernon, additional, Tarasov, Kirill V, additional, Müller, Martina, additional, Sotoodehnia, Nona, additional, Sinner, Moritz F, additional, Verwoert, Germaine C, additional, Li, Man, additional, Kao, W H Linda, additional, Köttgen, Anna, additional, Coresh, Josef, additional, Bis, Joshua C, additional, Psaty, Bruce M, additional, Rice, Kenneth, additional, Rotter, Jerome I, additional, Rivadeneira, Fernando, additional, Hofman, Albert, additional, Kors, Jan A, additional, Stricker, Bruno H C, additional, Uitterlinden, André G, additional, van Duijn, Cornelia M, additional, Beckmann, Britt M, additional, Sauter, Wiebke, additional, Gieger, Christian, additional, Lubitz, Steven A, additional, Newton-Cheh, Christopher, additional, Wang, Thomas J, additional, Magnani, Jared W, additional, Schnabel, Renate B, additional, Chung, Mina K, additional, Barnard, John, additional, Smith, Jonathan D, additional, Van Wagoner, David R, additional, Vasan, Ramachandran S, additional, Aspelund, Thor, additional, Eiriksdottir, Gudny, additional, Harris, Tamara B, additional, Launer, Lenore J, additional, Najjar, Samer S, additional, Lakatta, Edward, additional, Schlessinger, David, additional, Uda, Manuela, additional, Abecasis, Gonçalo R, additional, Müller-Myhsok, Bertram, additional, Ehret, Georg B, additional, Boerwinkle, Eric, additional, Chakravarti, Aravinda, additional, Soliman, Elsayed Z, additional, Lunetta, Kathryn L, additional, Perz, Siegfried, additional, Wichmann, H-Erich, additional, Meitinger, Thomas, additional, Levy, Daniel, additional, Gudnason, Vilmundur, additional, Ellinor, Patrick T, additional, Sanna, Serena, additional, Kääb, Stefan, additional, Witteman, Jacqueline C M, additional, Alonso, Alvaro, additional, Benjamin, Emelia J, additional, and Heckbert, Susan R, additional

Published
2010
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39. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

Author

Benjamin, Emelia J, primary, Rice, Kenneth M, additional, Arking, Dan E, additional, Pfeufer, Arne, additional, van Noord, Charlotte, additional, Smith, Albert V, additional, Schnabel, Renate B, additional, Bis, Joshua C, additional, Boerwinkle, Eric, additional, Sinner, Moritz F, additional, Dehghan, Abbas, additional, Lubitz, Steven A, additional, D'Agostino Sr, Ralph B, additional, Lumley, Thomas, additional, Ehret, Georg B, additional, Heeringa, Jan, additional, Aspelund, Thor, additional, Newton-Cheh, Christopher, additional, Larson, Martin G, additional, Marciante, Kristin D, additional, Soliman, Elsayed Z, additional, Rivadeneira, Fernando, additional, Wang, Thomas J, additional, Eiríksdottir, Gudny, additional, Levy, Daniel, additional, Psaty, Bruce M, additional, Li, Man, additional, Chamberlain, Alanna M, additional, Hofman, Albert, additional, Vasan, Ramachandran S, additional, Harris, Tamara B, additional, Rotter, Jerome I, additional, Kao, W H Linda, additional, Agarwal, Sunil K, additional, Stricker, Bruno H Ch, additional, Wang, Ke, additional, Launer, Lenore J, additional, Smith, Nicholas L, additional, Chakravarti, Aravinda, additional, Uitterlinden, André G, additional, Wolf, Philip A, additional, Sotoodehnia, Nona, additional, Köttgen, Anna, additional, van Duijn, Cornelia M, additional, Meitinger, Thomas, additional, Mueller, Martina, additional, Perz, Siegfried, additional, Steinbeck, Gerhard, additional, Wichmann, H-Erich, additional, Lunetta, Kathryn L, additional, Heckbert, Susan R, additional, Gudnason, Vilmundur, additional, Alonso, Alvaro, additional, Kääb, Stefan, additional, Ellinor, Patrick T, additional, and Witteman, Jacqueline C M, additional

Published
2009
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40. Common variants at ten loci modulate the QT interval duration in the QTSCD Study

Author

Pfeufer, Arne, primary, Sanna, Serena, additional, Arking, Dan E, additional, Müller, Martina, additional, Gateva, Vesela, additional, Fuchsberger, Christian, additional, Ehret, Georg B, additional, Orrú, Marco, additional, Pattaro, Cristian, additional, Köttgen, Anna, additional, Perz, Siegfried, additional, Usala, Gianluca, additional, Barbalic, Maja, additional, Li, Man, additional, Pütz, Benno, additional, Scuteri, Angelo, additional, Prineas, Ronald J, additional, Sinner, Moritz F, additional, Gieger, Christian, additional, Najjar, Samer S, additional, Kao, W H Linda, additional, Mühleisen, Thomas W., additional, Dei, Mariano, additional, Happle, Christine, additional, Möhlenkamp, Stefan, additional, Crisponi, Laura, additional, Erbel, Raimund, additional, Jöckel, Karl-Heinz, additional, Naitza, Silvia, additional, Steinbeck, Gerhard, additional, Marroni, Fabio, additional, Hicks, Andrew A, additional, Lakatta, Edward, additional, Müller-Myhsok, Bertram, additional, Pramstaller, Peter P, additional, Wichmann, H-Erich, additional, Schlessinger, David, additional, Boerwinkle, Eric, additional, Meitinger, Thomas, additional, Uda, Manuela, additional, Coresh, Josef, additional, Kääb, Stefan, additional, Abecasis, Gonçalo R, additional, and Chakravarti, Aravinda, additional

Published
2009
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41. Common Genetic Variants in ANK2 Modulate QT Interval

Author

Sedlacek, Kamil, primary, Stark, Klaus, additional, Cunha, Shane R., additional, Pfeufer, Arne, additional, Weber, Stefan, additional, Berger, Iris, additional, Perz, Siegfried, additional, Kääb, Stefan, additional, Wichmann, Hans-Erich, additional, Mohler, Peter J., additional, Hengstenberg, Christian, additional, and Jeron, Andreas, additional

Published
2008
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45. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization

Author

Arking, Dan E, primary, Pfeufer, Arne, additional, Post, Wendy, additional, Kao, W H Linda, additional, Newton-Cheh, Christopher, additional, Ikeda, Morna, additional, West, Kristen, additional, Kashuk, Carl, additional, Akyol, Mahmut, additional, Perz, Siegfried, additional, Jalilzadeh, Shapour, additional, Illig, Thomas, additional, Gieger, Christian, additional, Guo, Chao-Yu, additional, Larson, Martin G, additional, Wichmann, H Erich, additional, Marbán, Eduardo, additional, O'Donnell, Christopher J, additional, Hirschhorn, Joel N, additional, Kääb, Stefan, additional, Spooner, Peter M, additional, Meitinger, Thomas, additional, and Chakravarti, Aravinda, additional

Published
2006
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46. Common Variants in Myocardial Ion Channel Genes Modify the QT Interval in the General Population

Author

Pfeufer, Arne, primary, Jalilzadeh, Shapour, additional, Perz, Siegfried, additional, Mueller, Jakob C., additional, Hinterseer, Martin, additional, Illig, Thomas, additional, Akyol, Mahmut, additional, Huth, Cornelia, additional, Schöpfer-Wendels, Andreas, additional, Kuch, Bernhard, additional, Steinbeck, Gerhard, additional, Holle, Rolf, additional, Näbauer, Michael, additional, Wichmann, H. -Erich, additional, Meitinger, Thomas, additional, and Kääb, Stefan, additional

Published
2005
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48. Increases in Heart Rate during an Air Pollution Episode.

Author

Peters, Annette, Perz, Siegfried, Döring, Angela, Stieber, Jutta, Koenig, Wolfgang, and Wichmann, H.Erich

Subjects
*AIR pollution, *HEALTH, *CARDIOVASCULAR disease etiology, *PHYSIOLOGICAL effects of heat, *PHYSIOLOGICAL effects of sulfur dioxide, *AIR quality research, *HEART beat, *PHYSIOLOGY
Abstract

This paper assesses whether air pollution increases resting heart rates in 2, 681 men and women aged 25–64 years who participated in the MONICA (monitoring of trends and determinants in cardiovascular disease) Augsburg cohort. Increases in heart rate were observed during the air pollution episode in January 1985 compared with non-episode days adjusted for cardiovascular risk factors and meteorologic parameters. Consistently, heart rates were also elevated at high concentrations of sulfur dioxide, total suspended particulates, or carbon monoxide. Acceleration in heart rates indicates an altered autonomic control of the heart in association with air pollution, which may contribute to the observed health effects in association with air pollution. Am J Epidemiol 1999; 150: 1094-8. [ABSTRACT FROM PUBLISHER]

Published
2009

49. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Arking, Dan E., Pulit, Sara L., Crotti, Lia, van der Harst, Pim, Munroe, Patricia B., Koopmann, Tamara T., Sotoodehnia, Nona, Rossin, Elizabeth J., Morley, Michael, Wang, Xinchen, Johnson, Andrew D., Lundby, Alicia, Gudbjartsson, Daníel F., Noseworthy, Peter A., Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V., Dörr, Marcus, Müller-Nurasyid, Martina, Lahtinen, Annukka M., Nolte, Ilja M., Smith, Albert Vernon, Bis, Joshua C., Isaacs, Aaron, Newhouse, Stephen J., Evans, Daniel S., Post, Wendy S., Waggott, Daryl, Lyytikäinen, Leo-Pekka, Hicks, Andrew A., Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J., Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W., Naluai, Åsa T., Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G., Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A., Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D., Harris, Tamara B., Launer, Lenore J., Shuldiner, Alan R., Alonso, Alvaro, Bader, Joel S., Ehret, Georg, Huang, Hailiang, Kao, W.H. Linda, Strait, James B., Macfarlane, Peter W., Brown, Morris, Caulfield, Mark J., Samani, Nilesh J., Kronenberg, Florian, Willeit, Johann, Smith, J. Gustav, Greiser, Karin H., zu Schwabedissen, Henriette Meyer, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R., Psaty, Bruce M., Rotter, Jerome I., Kolcic, Ivana, Polašek, Ozren, Wright, Alan F., Griffin, Maura, Daly, Mark J., Arnar, David O., Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C., Roden, Dan M., Zuvich, Rebecca L., Emilsson, Valur, Plump, Andrew S., Larson, Martin G., O'Donnell, Christopher J., Yin, Xiaoyan, Bobbo, Marco, D'Adamo, Adamo P., Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R., Nalls, Michael A., Jula, Antti, Kontula, Kimmo K., Marjamaa, Annukka, Oikarinen, Lasse, Perola, Markus, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl-Heinz, Kälsch, Hagen, Nöthen, Markus M., consortium, HRGEN, den Hoed, Marcel, Loos, Ruth J.F., Thelle, Dag S., Gieger, Christian, Meitinger, Thomas, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F., Waldenberger, Melanie, de Boer, Rudolf A., Franke, Lude, van der Vleuten, Pieter A., Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A.M., Behr, Elijah R., Dalageorgou, Chrysoula, Giudicessi, John R., Medeiros-Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M., Scherer, Stephen W., Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E., Fabiola Del, Greco M., Fuchsberger, Christian, O'Connell, Jeffrey R., Lee, Wai K., Watt, Graham C.M., Campbell, Harry, Wild, Sarah H., El Mokhtari, Nour E., Frey, Norbert, Asselbergs, Folkert W., Leach, Irene Mateo, Navis, Gerjan, van den Berg, Maarten P., van Veldhuisen, Dirk J., Kellis, Manolis, Krijthe, Bouwe P., Franco, Oscar H., Hofman, Albert, Kors, Jan A., Uitterlinden, André G., Witteman, Jacqueline C.M., Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A., Abecasis, Gonçalo R., Lakatta, Edward G., Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R.P., Völker, Uwe, Snieder, Harold, Spector, Timothy D., Ärnlöv, Johan, Lind, Lars, Sundström, Johan, Syvänen, Ann-Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T., Viikari, Jorma S., Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N., Paulweber, Bernhard, Haerting, Johannes, Dominiczak, Anna F., Nyberg, Fredrik, Whincup, Peter H., Hingorani, Aroon, Schott, Jean-Jacques, Bezzina, Connie R., Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F., Rudan, Igor, Franke, Andre, Mühleisen, Thomas W., Pramstaller, Peter P., Lehtimäki, Terho J., Paterson, Andrew D., Parsa, Afshin, Liu, Yongmei, van Duijn, Cornelia, Siscovick, David S., Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B., Sanna, Serena, Ritchie, Marylyn D., Stricker, Bruno H., Stefansson, Kari, Boyer, Laurie A., Cappola, Thomas P., Olsen, Jesper V., Lage, Kasper, Schwartz, Peter J., Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J., Pfeufer, Arne, de Bakker, Paul I.W., and Newton-Cheh, Christopher

Subjects
genome-wide association study, QT interval, Long QT Syndrome, sudden cardiac death, myocardial repolarization, arrhythmias
Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD.

Published
2014
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50. A Large Candidate Gene Survey Identifies the KCNE1D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes

Author

Kääb, Stefan, Crawford, Dana C., Sinner, Moritz F., Behr, Elijah R., Kannankeril, Prince J., Wilde, Arthur A.M., Bezzina, Connie R., Schulze-Bahr, Eric, Guicheney, Pascale, Bishopric, Nanette H., Myerburg, Robert J., Schott, Jean-Jacques, Pfeufer, Arne, Beckmann, Britt-Maria, Martens, Eimo, Zhang, Taifang, Stallmeyer, Birgit, Zumhagen, Sven, Denjoy, Isabelle, Bardai, Abdennasser, Gelder, Isabelle C. Van, Jamshidi, Yalda, Dalageorgou, Chrysoula, Marshall, Vanessa, Jeffery, Steve, Shakir, Saad, Camm, A. John, Steinbeck, Gerhard, Perz, Siegfried, Lichtner, Peter, Meitinger, Thomas, Peters, Annette, Wichmann, H.-Erich, Ingram, Christiana, Bradford, Yuki, Carter, Shannon, Norris, Kris, Ritchie, Marylyn D., George, Alfred L., and Roden, Dan M.

Abstract

Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS.

Published
2012
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