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1. Human genetic structure in Northwest France provides new insights into West European historical demography

Author

Alves, Isabel, Giemza, Joanna, Blum, Michael G. B., Bernhardsson, Carolina, Chatel, Stéphanie, Karakachoff, Matilde, Saint Pierre, Aude, Herzig, Anthony F., Olaso, Robert, Monteil, Martial, Gallien, Véronique, Cabot, Elodie, Svensson, Emma, Bacq, Delphine, Baron, Estelle, Berthelier, Charlotte, Besse, Céline, Blanché, Hélène, Bocher, Ozvan, Boland, Anne, Bonnaud, Stéphanie, Charpentier, Eric, Dandine-Roulland, Claire, Férec, Claude, Fruchet, Christine, Lecointe, Simon, Le Floch, Edith, Ludwig, Thomas E., Marenne, Gaëlle, Meyer, Vincent, Quellery, Elisabeth, Racimo, Fernando, Rouault, Karen, Sandron, Florian, Schott, Jean-Jacques, Velo-Suarez, Lourdes, Violleau, Jade, Willerslev, Eske, Coativy, Yves, Jézéquel, Mael, Le Bris, Daniel, Nicolas, Clément, Pailler, Yvan, Goldberg, Marcel, Zins, Marie, Le Marec, Hervé, Jakobsson, Mattias, Darlu, Pierre, Génin, Emmanuelle, Deleuze, Jean-François, Redon, Richard, and Dina, Christian

Published
2024
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2. TAD boundary deletion causes PITX2-related cardiac electrical and structural defects

Author

Baudic, Manon, Murata, Hiroshige, Bosada, Fernanda M., Melo, Uirá Souto, Aizawa, Takanori, Lindenbaum, Pierre, van der Maarel, Lieve E., Guedon, Amaury, Baron, Estelle, Fremy, Enora, Foucal, Adrien, Ishikawa, Taisuke, Ushinohama, Hiroya, Jurgens, Sean J., Choi, Seung Hoan, Kyndt, Florence, Le Scouarnec, Solena, Wakker, Vincent, Thollet, Aurélie, Rajalu, Annabelle, Takaki, Tadashi, Ohno, Seiko, Shimizu, Wataru, Horie, Minoru, Kimura, Takeshi, Ellinor, Patrick T., Petit, Florence, Dulac, Yves, Bru, Paul, Boland, Anne, Deleuze, Jean-François, Redon, Richard, Le Marec, Hervé, Le Tourneau, Thierry, Gourraud, Jean-Baptiste, Yoshida, Yoshinori, Makita, Naomasa, Vieyres, Claude, Makiyama, Takeru, Mundlos, Stephan, Christoffels, Vincent M., Probst, Vincent, Schott, Jean-Jacques, and Barc, Julien

Published
2024
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3. A Rare Noncoding Enhancer Variant in SCN5A Contributes to the High Prevalence of Brugada Syndrome in Thailand

Author

Walsh, Roddy, Mauleekoonphairoj, John, Mengarelli, Isabella, Bosada, Fernanda M., Verkerk, Arie O., van Duijvenboden, Karel, Poovorawan, Yong, Wongcharoen, Wanwarang, Sutjaporn, Boosamas, Wandee, Pharawee, Chimparlee, Nitinan, Chokesuwattanaskul, Ronpichai, Vongpaisarnsin, Kornkiat, Dangkao, Piyawan, Wu, Cheng-I, Tadros, Rafik, Amin, Ahmad S., Lieve, Krystien V.V., Postema, Pieter G., Kooyman, Maarten, Beekman, Leander, Sahasatas, Dujdao, Amnueypol, Montawatt, Krittayaphong, Rungroj, Prechawat, Somchai, Anannab, Alisara, Makarawate, Pattarapong, Ngarmukos, Tachapong, Phusanti, Keerapa, Veerakul, Gumpanart, Kingsbury, Zoya, Newington, Taksina, Maheswari, Uma, Ross, Mark T., Grace, Andrew, Lambiase, Pier D., Behr, Elijah R., Schott, Jean-Jacques, Redon, Richard, Barc, Julien, Christoffels, Vincent M., Wilde, Arthur A.M., Nademanee, Koonlawee, Bezzina, Connie R., and Khongphatthanayothin, Apichai

Published
2024
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4. Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study

Author

Chen, Hao Yu, Dina, Christian, Small, Aeron M, Shaffer, Christian M, Levinson, Rebecca T, Helgadóttir, Anna, Capoulade, Romain, Munter, Hans Markus, Martinsson, Andreas, Cairns, Benjamin J, Trudsø, Linea C, Hoekstra, Mary, Burr, Hannah A, Marsh, Thomas W, Damrauer, Scott M, Dufresne, Line, Le Scouarnec, Solena, Messika-Zeitoun, David, Ranatunga, Dilrini K, Whitmer, Rachel A, Bonnefond, Amélie, Sveinbjornsson, Garðar, Daníelsen, Ragnar, Arnar, David O, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Gudbjartsson, Daníel F, Hólm, Hilma, Ghouse, Jonas, Olesen, Morten Salling, Christensen, Alex H, Mikkelsen, Susan, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, Erikstrup, Christian, Ostrowski, Sisse R, Center, Regeneron Genetics, O’Donnell, Christopher J, Budoff, Matthew J, Gudnason, Vilmundur, Post, Wendy S, Rotter, Jerome I, Lathrop, Mark, Bundgaard, Henning, Johansson, Bengt, Ljungberg, Johan, Näslund, Ulf, Le Tourneau, Thierry, Smith, J Gustav, Wells, Quinn S, Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J, Clarke, Robert, Engert, James C, and Thanassoulis, George

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease - Coronary Heart Disease, Prevention, Heart Disease, Cardiovascular, Genetics, Human Genome, Atherosclerosis, 2.1 Biological and endogenous factors, Humans, Genome-Wide Association Study, Adiposity, Genetic Predisposition to Disease, Aortic Valve Stenosis, Obesity, Risk Factors, Inflammation, Dyslipidemias, Apolipoproteins, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Aortic stenosis, Genome-wide association study, Mendelian randomization, Phenome-wide association study, Gene expression, Genetic risk score, Regeneron Genetics Center, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

AimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.Methods and resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

Published
2023

6. Left Ventricular Abnormal Substrate in Brugada Syndrome

Author

Cheniti, Ghassen, Haissaguerre, Michel, Dina, Christian, Kamakura, Tsukasa, Duchateau, Josselin, Sacher, Frederic, Racine, Hugo-Pierre, Surget, Elodie, Simonet, Floriane, Gourraud, Jean-Baptiste, Sridi, Soumaya, Cochet, Hubert, Andre, Clementine, Bouyer, Benjamin, Chauvel, Remi, Tixier, Romain, Derval, Nicolas, Pambrun, Thomas, Dubois, Remi, Jais, Pierre, Nademanee, Koonlawee, Redon, Richard, Schott, Jean-Jacques, Probst, Vincent, Hocini, Meleze, Barc, Julien, and Bernus, Olivier

Published
2023
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7. Machine Learning–Based Phenogrouping in MVP Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events

Author

Huttin, Olivier, Girerd, Nicolas, Jobbe-Duval, Antoine, Constant Dit Beaufils, Anne-Laure, Senage, Thomas, Filippetti, Laura, Cueff, Caroline, Duarte, Kevin, Fraix, Antoine, Piriou, Nicolas, Mandry, Damien, Pace, Nathalie, Le Scouarnec, Solena, Capoulade, Romain, Echivard, Matthieu, Sellal, Jean Marc, Marrec, Marie, Beaumont, Marine, Hossu, Gabriella, Trochu, Jean-Noel, Sadoul, Nicolas, Marie, Pierre-Yves, Guenancia, Charles, Schott, Jean-Jacques, Roussel, Jean-Christian, Serfaty, Jean-Michel, Selton-Suty, Christine, and Le Tourneau, Thierry

Published
2023
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8. Functional Epicardial Conduction Disturbances Due to a SCN5A Variant Associated With Brugada Syndrome

Author

Renard, Estelle, Walton, Richard D., Benoist, David, Brette, Fabien, Bru-Mercier, Gilles, Chaigne, Sébastien, Charron, Sabine, Constantin, Marion, Douard, Matthieu, Dubes, Virginie, Guillot, Bastien, Hof, Thomas, Magat, Julie, Martinez, Marine E., Michel, Cindy, Pallares-Lupon, Néstor, Pasdois, Philippe, Récalde, Alice, Vaillant, Fanny, Sacher, Frédéric, Labrousse, Louis, Rogier, Julien, Kyndt, Florence, Baudic, Manon, Schott, Jean-Jacques, Barc, Julien, Probst, Vincent, Sarlandie, Marine, Marionneau, Céline, Ashton, Jesse L., Hocini, Mélèze, Haïssaguerre, Michel, and Bernus, Olivier

Published
2023
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11. Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author

Barc, Julien, Tadros, Rafik, Glinge, Charlotte, Chiang, David Y., Jouni, Mariam, Simonet, Floriane, Jurgens, Sean J., Baudic, Manon, Nicastro, Michele, Potet, Franck, Offerhaus, Joost A., Walsh, Roddy, Choi, Seung Hoan, Verkerk, Arie O., Mizusawa, Yuka, Anys, Soraya, Minois, Damien, Arnaud, Marine, Duchateau, Josselin, Wijeyeratne, Yanushi D., Muir, Alison, Papadakis, Michael, Castelletti, Silvia, Torchio, Margherita, Ortuño, Cristina Gil, Lacunza, Javier, Giachino, Daniela F., Cerrato, Natascia, Martins, Raphaël P., Campuzano, Oscar, Van Dooren, Sonia, Thollet, Aurélie, Kyndt, Florence, Mazzanti, Andrea, Clémenty, Nicolas, Bisson, Arnaud, Corveleyn, Anniek, Stallmeyer, Birgit, Dittmann, Sven, Saenen, Johan, Noël, Antoine, Honarbakhsh, Shohreh, Rudic, Boris, Marzak, Halim, Rowe, Matthew K., Federspiel, Claire, Le Page, Sophie, Placide, Leslie, Milhem, Antoine, Barajas-Martinez, Hector, Beckmann, Britt-Maria, Krapels, Ingrid P., Steinfurt, Johannes, Winkel, Bo Gregers, Jabbari, Reza, Shoemaker, Moore B., Boukens, Bas J., Škorić-Milosavljević, Doris, Bikker, Hennie, Manevy, Federico C., Lichtner, Peter, Ribasés, Marta, Meitinger, Thomas, Müller-Nurasyid, Martina, Veldink, Jan H., van den Berg, Leonard H., Van Damme, Philip, Cusi, Daniele, Lanzani, Chiara, Rigade, Sidwell, Charpentier, Eric, Baron, Estelle, Bonnaud, Stéphanie, Lecointe, Simon, Donnart, Audrey, Le Marec, Hervé, Chatel, Stéphanie, Karakachoff, Matilde, Bézieau, Stéphane, London, Barry, Tfelt-Hansen, Jacob, Roden, Dan, Odening, Katja E., Cerrone, Marina, Chinitz, Larry A., Volders, Paul G., van de Berg, Maarten P., Laurent, Gabriel, Faivre, Laurence, Antzelevitch, Charles, Kääb, Stefan, Arnaout, Alain Al, Dupuis, Jean-Marc, Pasquie, Jean-Luc, Billon, Olivier, Roberts, Jason D., Jesel, Laurence, Borggrefe, Martin, Lambiase, Pier D., Mansourati, Jacques, Loeys, Bart, Leenhardt, Antoine, Guicheney, Pascale, Maury, Philippe, Schulze-Bahr, Eric, Robyns, Tomas, Breckpot, Jeroen, Babuty, Dominique, Priori, Silvia G., Napolitano, Carlo, de Asmundis, Carlo, Brugada, Pedro, Brugada, Ramon, Arbelo, Elena, Brugada, Josep, Mabo, Philippe, Behar, Nathalie, Giustetto, Carla, Molina, Maria Sabater, Gimeno, Juan R., Hasdemir, Can, Schwartz, Peter J., Crotti, Lia, McKeown, Pascal P., Sharma, Sanjay, Behr, Elijah R., Haissaguerre, Michel, Sacher, Frédéric, Rooryck, Caroline, Tan, Hanno L., Remme, Carol A., Postema, Pieter G., Delmar, Mario, Ellinor, Patrick T., Lubitz, Steven A., Gourraud, Jean-Baptiste, Tanck, Michael W., George, Jr., Alfred L., MacRae, Calum A., Burridge, Paul W., Dina, Christian, Probst, Vincent, Wilde, Arthur A., Schott, Jean-Jacques, Redon, Richard, and Bezzina, Connie R.

Published
2022
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12. Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci

Author

Ishikawa, Taisuke, primary, Masuda, Tatsuo, additional, Hachiya, Tsuyoshi, additional, Dina, Christian, additional, Simonet, Floriane, additional, Nagata, Yuki, additional, Tanck, Michael W T, additional, Sonehara, Kyuto, additional, Glinge, Charlotte, additional, Tadros, Rafik, additional, Khongphatthanayothin, Apichai, additional, Lu, Tzu-Pin, additional, Higuchi, Chihiro, additional, Nakajima, Tadashi, additional, Hayashi, Kenshi, additional, Aizawa, Yoshiyasu, additional, Nakano, Yukiko, additional, Nogami, Akihiko, additional, Morita, Hiroshi, additional, Ohno, Seiko, additional, Aiba, Takeshi, additional, Juárez, Christian Krijger, additional, Mauleekoonphairoj, John, additional, Poovorawan, Yong, additional, Gourraud, Jean-Baptiste, additional, Shimizu, Wataru, additional, Probst, Vincent, additional, Horie, Minoru, additional, Wilde, Arthur A M, additional, Redon, Richard, additional, Juang, Jyh-Ming Jimmy, additional, Nademanee, Koonlawee, additional, Bezzina, Connie R, additional, Barc, Julien, additional, Tanaka, Toshihiro, additional, Okada, Yukinori, additional, Schott, Jean-Jacques, additional, and Makita, Naomasa, additional

Published
2024
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13. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls

Author

Walsh, Roddy, Lahrouchi, Najim, Tadros, Rafik, Kyndt, Florence, Glinge, Charlotte, Postema, Pieter G., Amin, Ahmad S., Nannenberg, Eline A., Ware, James S., Whiffin, Nicola, Mazzarotto, Francesco, Škorić-Milosavljević, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bézieau, Stéphane, Bos, J. Martijn, Breckpot, Jeroen, Campuzano, Oscar, Castelletti, Silvia, Celen, Candan, Clauss, Sebastian, Corveleyn, Anniek, Crotti, Lia, Dagradi, Federica, de Asmundis, Carlo, Denjoy, Isabelle, Dittmann, Sven, Ellinor, Patrick T., Ortuño, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jørgen K., Kimoto, Hiroki, Kotta, Maria-Christina, Krapels, Ingrid P.C., Kurabayashi, Masahiko, Lazarte, Julieta, Leenhardt, Antoine, Loeys, Bart L., Lundin, Catarina, Makiyama, Takeru, Mansourati, Jacques, Martins, Raphaël P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frédéric, Sahin, Hatice, Sarquella-Brugada, Georgia, Sebastiano, Regina, Sharma, Sanjay, Sheppard, Mary N., Shimamoto, Keiko, Shoemaker, M.Benjamin, Stallmeyer, Birgit, Steinfurt, Johannes, Tanaka, Yuji, Tester, David J., Usuda, Keisuke, van der Zwaag, Paul A., Van Dooren, Sonia, Van Laer, Lut, Winbo, Annika, Winkel, Bo G., Yamagata, Kenichiro, Zumhagen, Sven, Volders, Paul G.A., Lubitz, Steven A., Antzelevitch, Charles, Platonov, Pyotr G., Odening, Katja E., Roden, Dan M., Roberts, Jason D., Skinner, Jonathan R., Tfelt-Hansen, Jacob, van den Berg, Maarten P., Olesen, Morten S., Lambiase, Pier D., Borggrefe, Martin, Hayashi, Kenshi, Rydberg, Annika, Nakajima, Tadashi, Yoshinaga, Masao, Saenen, Johan B., Kääb, Stefan, Brugada, Pedro, Robyns, Tomas, Giachino, Daniela F., Ackerman, Michael J., Brugada, Ramon, Brugada, Josep, Gimeno, Juan R., Hasdemir, Can, Guicheney, Pascale, Priori, Silvia G., Schulze-Bahr, Eric, Makita, Naomasa, Schwartz, Peter J., Shimizu, Wataru, Aiba, Takeshi, Schott, Jean-Jacques, Redon, Richard, Ohno, Seiko, Probst, Vincent, Arnaout, Alain Al, Amelot, Mathieu, Anselme, Frédéric, Billon, Olivier, Defaye, Pascal, Dupuis, Jean-Marc, Jesel, Laurence, Laurent, Gabriel, Maury, Philippe, Pasquie, Jean-Luc, Wiart, Francois, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.

Published
2021
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14. Exploring the origins of neurodevelopmental proteasomopathies associated with cardiac malformations: are neural crest cells central to certain pathological mechanisms?

Author

Vignard, Virginie, Baruteau, Alban-Elouen, Toutain, Bérénice, Mercier, Sandra, Isidor, Bertrand, Redon, Richard, Schott, Jean-Jacques, Küry, Sébastien, Bézieau, Stéphane, Monsoro-Burq, Anne H., and Ebstein, Frédéric

Subjects
NEURAL crest, NEURAL development, HUMAN abnormalities, PROTEASOMES, HOMEOSTASIS
Abstract

Neurodevelopmental proteasomopathies constitute a recently defined class of rare Mendelian disorders, arising from genomic alterations in proteasome-related genes. These alterations result in the dysfunction of proteasomes, which are multi-subunit protein complexes essential for maintaining cellular protein homeostasis. The clinical phenotype of these diseases manifests as a syndromic association involving impaired neural development and multisystem abnormalities, notably craniofacial anomalies and malformations of the cardiac outflow tract (OFT). These observations suggest that proteasome loss-offunction variants primarily affect specific embryonic cell types which serve as origins for both craniofacial structures and the conotruncal portion of the heart. In this hypothesis article, we propose that neural crest cells (NCCs), a highly multipotent cell population, which generates craniofacial skeleton, mesenchyme as well as the OFT of the heart, in addition to many other derivatives, would exhibit a distinctive vulnerability to protein homeostasis perturbations. Herein, we introduce the diverse cellular compensatory pathways activated in response to protein homeostasis disruption and explore their potential implications for NCC physiology. Altogether, the paper advocates for investigating proteasome biology within NCCs and their early cranial and cardiac derivatives, offering a rationale for future exploration and laying the initial groundwork for therapeutic considerations. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis

Author

Perrot, Nicolas, Valerio, Vincenza, Moschetta, Donato, Boekholdt, S. Matthijs, Dina, Christian, Chen, Hao Yu, Abner, Erik, Martinsson, Andreas, Manikpurage, Hasanga D., Rigade, Sidwell, Capoulade, Romain, Mass, Elvira, Clavel, Marie-Annick, Le Tourneau, Thierry, Messika-Zeitoun, David, Wareham, Nicholas J., Engert, James C., Polvani, Gianluca, Pibarot, Philippe, Esko, Tõnu, Smith, J. Gustav, Mathieu, Patrick, Thanassoulis, George, Schott, Jean-Jacques, Bossé, Yohan, Camera, Marina, Thériault, Sébastien, Poggio, Paolo, and Arsenault, Benoit J.

Published
2020
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17. Genetic association analyses highlight biological pathways underlying mitral valve prolapse

Author

Dina, Christian, Bouatia-Naji, Nabila, Tucker, Nathan, Delling, Francesca N, Toomer, Katelynn, Durst, Ronen, Perrocheau, Maelle, Fernandez-Friera, Leticia, Solis, Jorge, Le Tourneau, Thierry, Chen, Ming-Huei, Probst, Vincent, Bosse, Yohan, Pibarot, Philippe, Zelenika, Diana, Lathrop, Mark, Hercberg, Serge, Roussel, Ronan, Benjamin, Emelia J, Bonnet, Fabrice, Lo, Su Hao, Dolmatova, Elena, Simonet, Floriane, Lecointe, Simon, Kyndt, Florence, Redon, Richard, Le Marec, Hervé, Froguel, Philippe, Ellinor, Patrick T, Vasan, Ramachandran S, Bruneval, Patrick, Markwald, Roger R, Norris, Russell A, Milan, David J, Slaugenhaupt, Susan A, Levine, Robert A, Schott, Jean-Jacques, Hagege, Albert A, and Jeunemaitre, Xavier

Subjects
Cardiovascular, Genetics, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Animals, Case-Control Studies, Genome-Wide Association Study, Humans, Mice, Mitral Valve Prolapse, PROMESA investigators, MVP-France, Leducq Transatlantic MITRAL Network, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair.

Published
2015

19. Filamin A heart valve disease as a genetic cause of inherited bicuspid and tricuspid aortic valve disease

Author

Delwarde, Constance, primary, Toquet, Claire, additional, Boureau, Anne Sophie, additional, Le Ruz, Robin, additional, Le Scouarnec, Solena, additional, Mérot, Jean, additional, Kyndt, Florence, additional, Bernstein, Daniel, additional, Bernstein, Jonathan A, additional, Aalberts, Jan J J, additional, Le Marec, Hervé, additional, Schott, Jean-Jacques, additional, Roussel, Jean-Christian, additional, Le Tourneau, Thierry, additional, and Capoulade, Romain, additional

Published
2023
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20. A rare non-coding enhancer variant in SCN5A contributes to the high prevalence of Brugada syndrome in Thailand

Author

Walsh, Roddy, primary, Mauleekoonphairoj, John, additional, Mengarelli, Isabella, additional, Verkerk, Arie O., additional, Bosada, Fernanda M., additional, van Duijvenboden, Karel, additional, Poovorawan, Yong, additional, Wongcharoen, Wanwarang, additional, Sutjaporn, Boosamas, additional, Wandee, Pharawee, additional, Chimparlee, Nitinan, additional, Chokesuwattanaskul, Ronpichai, additional, Vongpaisarnsin, Kornkiat, additional, Dangkao, Piyawan, additional, Wu, Cheng-I, additional, Tadros, Rafik, additional, Amin, Ahmad S., additional, Lieve, Krystien V.V., additional, Postema, Pieter G., additional, Kooyman, Maarten, additional, Beekman, Leander, additional, Phusanti, Keerapa, additional, Sahasatas, Dujdao, additional, Amnueypol, Montawatt, additional, Krittayaphong, Rungroj, additional, Prechawat, Somchai, additional, Anannab, Alisara, additional, Makarawate, Pattarapong, additional, Ngarmukos, Tachapong, additional, Veerakul, Gumpanart, additional, Kingsbury, Zoya, additional, Newington, Taksina, additional, Maheswari, Uma, additional, Ross, Mark T., additional, Grace, Andrew, additional, Lambiase, Pier D., additional, Behr, Elijah R., additional, Schott, Jean-Jacques, additional, Redon, Richard, additional, Barc, Julien, additional, Christoffels, Vincent M., additional, Wilde, Arthur A.M., additional, Nademanee, Koonlawee, additional, Bezzina, Connie R., additional, and Khongphatthanayothin, Apichai, additional

Published
2023
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21. Author Correction: Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author

Barc, Julien, Tadros, Rafik, Glinge, Charlotte, Chiang, David Y., Jouni, Mariam, Simonet, Floriane, Jurgens, Sean J., Baudic, Manon, Nicastro, Michele, Potet, Franck, Offerhaus, Joost A., Walsh, Roddy, Choi, Seung Hoan, Verkerk, Arie O., Mizusawa, Yuka, Anys, Soraya, Minois, Damien, Arnaud, Marine, Duchateau, Josselin, Wijeyeratne, Yanushi D., Muir, Alison, Papadakis, Michael, Castelletti, Silvia, Torchio, Margherita, Ortuño, Cristina Gil, Lacunza, Javier, Giachino, Daniela F., Cerrato, Natascia, Martins, Raphaël P., Campuzano, Oscar, Van Dooren, Sonia, Thollet, Aurélie, Kyndt, Florence, Mazzanti, Andrea, Clémenty, Nicolas, Bisson, Arnaud, Corveleyn, Anniek, Stallmeyer, Birgit, Dittmann, Sven, Saenen, Johan, Noël, Antoine, Honarbakhsh, Shohreh, Rudic, Boris, Marzak, Halim, Rowe, Matthew K., Federspiel, Claire, Le Page, Sophie, Placide, Leslie, Milhem, Antoine, Barajas-Martinez, Hector, Beckmann, Britt-Maria, Krapels, Ingrid P., Steinfurt, Johannes, Winkel, Bo Gregers, Jabbari, Reza, Shoemaker, Moore B., Boukens, Bas J., Škorić-Milosavljević, Doris, Bikker, Hennie, Manevy, Federico, Lichtner, Peter, Ribasés, Marta, Meitinger, Thomas, Müller-Nurasyid, Martina, Veldink, Jan H., van den Berg, Leonard H., Van Damme, Philip, Cusi, Daniele, Lanzani, Chiara, Rigade, Sidwell, Charpentier, Eric, Baron, Estelle, Bonnaud, Stéphanie, Lecointe, Simon, Donnart, Audrey, Le Marec, Hervé, Chatel, Stéphanie, Karakachoff, Matilde, Bézieau, Stéphane, London, Barry, Tfelt-Hansen, Jacob, Roden, Dan, Odening, Katja E., Cerrone, Marina, Chinitz, Larry A., Volders, Paul G., van de Berg, Maarten P., Laurent, Gabriel, Faivre, Laurence, Antzelevitch, Charles, Kääb, Stefan, Arnaout, Alain Al, Dupuis, Jean-Marc, Pasquie, Jean-Luc, Billon, Olivier, Roberts, Jason D., Jesel, Laurence, Borggrefe, Martin, Lambiase, Pier D., Mansourati, Jacques, Loeys, Bart, Leenhardt, Antoine, Guicheney, Pascale, Maury, Philippe, Schulze-Bahr, Eric, Robyns, Tomas, Breckpot, Jeroen, Babuty, Dominique, Priori, Silvia G., Napolitano, Carlo, de Asmundis, Carlo, Brugada, Pedro, Brugada, Ramon, Arbelo, Elena, Brugada, Josep, Mabo, Philippe, Behar, Nathalie, Giustetto, Carla, Molina, Maria Sabater, Gimeno, Juan R., Hasdemir, Can, Schwartz, Peter J., Crotti, Lia, McKeown, Pascal P., Sharma, Sanjay, Behr, Elijah R., Haissaguerre, Michel, Sacher, Frédéric, Rooryck, Caroline, Tan, Hanno L., Remme, Carol A., Postema, Pieter G., Delmar, Mario, Ellinor, Patrick T., Lubitz, Steven A., Gourraud, Jean-Baptiste, Tanck, Michael W., George, Jr., Alfred L., MacRae, Calum A., Burridge, Paul W., Dina, Christian, Probst, Vincent, Wilde, Arthur A., Schott, Jean-Jacques, Redon, Richard, and Bezzina, Connie R.

Published
2022
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22. Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm

Author

Desal, Hubert, Bourcier, Romain, Daumas-Duport, Benjamin, Isidor, Bertrand, Connault, Jérôme, Lebranchu, Pierre, Le Tourneau, Thierry, Viarouge, Marie Pierre, Papagiannaki, Chrisanthi, Piotin, Michel, Redjem, Hocine, Mazighi, Mikael, Desilles, Jean Philippe, Naggara, Olivier, Trystram, Denis, Edjlali-Goujon, Myriam, Rodriguez, Christine, Ben Hassen, Waghi, Saleme, Suzanna, Mounayer, Charbel, Levrier, Olivier, Aguettaz, Pierre, Combaz, Xavier, Pasco, Anne, Berthier, Emeline, Bintner, Marc, Molho, Marc, Gauthier, Pascale, Chivot, Cyril, Costalat, Vincent, Darganzil, Cyril, Bonafé, Alain, Januel, Anne Christine, Michelozzi, Caterina, Cognard, Christophe, Bonneville, Fabrice, Tall, Philippe, Darcourt, Jean, Biondi, Alessandra, Iosif, Cristina, Pomero, Elisa, Ferre, Jean Christophe, Gauvrit, Jean Yves, Eugene, François, Raoult, Hélène, Gentric, Jean Christophe, Ognard, Julien, Anxionnat, René, Bracard, Serge, Derelle, Anne Laure, Tonnelet, Romain, Spelle, Laurent, Ikka, Léon, Fahed, Robert, Rouchaud, Aymeric, Ozanne, Augustin, Caroff, Jildaz, Ben Achour, Nidal, Moret, Jacques, Chabert, Emmanuel, Berge, Jérôme, Marnat, Gaultier, Barreau, Xavier, Gariel, Florent, Clarencon, Frédéric, Aggour, Mohammed, Ricolfi, Frédéric, Chavent, Adrien, Thouant, Pierre, Lebidinsky, Pablo, Lemogne, Brivael, Herbreteau, Denis, Bibi, Richard, Pierot, Laurent, Soize, Sébastien, Labeyrie, Marc Antoine, Vandendries, Christophe, Houdart, Emmanuel, Kazemi, Appoline, Leclerc, Xavier, Pruvo, Jean Pierre, Gallas, Sophie, Velasco, Stéphane, Le Scouarnec, Solena, Bonnaud, Stéphanie, Karakachoff, Matilde, Bourcereau, Emmanuelle, Heurtebise-Chrétien, Sandrine, Menguy, Céline, Dina, Christian, Simonet, Floriane, Moles, Alexis, Lenoble, Cédric, Lindenbaum, Pierre, Chatel, Stéphanie, Génin, Emmanuelle, Deleuze, Jean-François, Schott, Jean-Jacques, Le Marec, Hervé, Loirand, Gervaise, and Redon, Richard

Published
2018
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23. Cardiac Emerinopathy: A Non-syndromic Nuclear Envelopathy with Increased Risk of Thromboembolic Stroke due to Progressive Atrial Standstill and Left Ventricular Non-compaction

Author

Ishikawa, Taisuke, Mishima, Hiroyuki, Barc, Julien, Takahashi, Masanori P., Hirono, Keiichi, Terada, Shigenori, Kowase, Shinya, Sato, Teruki, Mukai, Yasushi, Yui, Yoshiaki, Ohkubo, Kimie, Kimoto, Hiroki, Watanabe, Hiroyuki, Hata, Yukiko, Aiba, Takeshi, Ohno, Seiko, Chishaki, Akiko, Shimizu, Wataru, Horie, Minoru, Ichida, Fukiko, Nogami, Akihiko, Yoshiura, Koh-Ichiro, Schott, Jean-Jacques, and Makita, Naomasa

Published
2020
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24. Sodium-channel blocker challenge in the familial screening of Brugada syndrome: Safety and predictors of positivity

Author

Therasse, Dylan, Sacher, Frederic, Petit, Bertrand, Babuty, Dominique, Mabo, Philippe, Martins, Raphael, Jesel, Laurence, Maury, Philippe, Pasquie, Jean Luc, Mansourati, Jacques, Dupuis, Jean Marc, Kyndt, Florence, Thollet, Aurélie, Guyomarch, Beatrice, Barc, Julien, Schott, Jean Jacques, Le Marec, Herve, Redon, Richard, Probst, Vincent, and Gourraud, Jean-Baptiste

Published
2017
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26. Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

Author

Lahrouchi, Najim, Tadros, Rafik, Crotti, Lia, Mizusawa, Yuka, Postema, Pieter G., Beekman, Leander, Walsh, Roddy, Hasegawa, Kanae, Barc, Julien, Ernsting, Marko, Turkowski, Kari L., Mazzanti, Andrea, Beckmann, Britt M., Shimamoto, Keiko, Diamant, Ulla-Britt, Wijeyeratne, Yanushi D., Kucho, Yu, Robyns, Tomas, Ishikawa, Taisuke, Arbelo, Elena, Christiansen, Michael, Winbo, Annika, Jabbari, Reza, Lubitz, Steven A., Steinfurt, Johannes, Rudic, Boris, Loeys, Bart, Shoemaker, M. Ben, Weeke, Peter E., Pfeiffer, Ryan, Davies, Brianna, Andorin, Antoine, Hofman, Nynke, Dagradi, Federica, Pedrazzini, Matteo, Tester, David J., Bos, J. Martijn, Sarquella-Brugada, Georgia, Campuzano, Óscar, Platonov, Pyotr G., Stallmeyer, Birgit, Zumhagen, Sven, Nannenberg, Eline A., Veldink, Jan H., van den Berg, Leonard H., Al-Chalabi, Ammar, Shaw, Christopher E., Shaw, Pamela J., Morrison, Karen E., Andersen, Peter M., Müller-Nurasyid, Martina, Cusi, Daniele, Barlassina, Cristina, Galan, Pilar, Lathrop, Mark, Munter, Markus, Werge, Thomas, Ribasés, Marta, Aung, Tin, Khor, Chiea C., Ozaki, Mineo, Lichtner, Peter, Meitinger, Thomas, van Tintelen, J. Peter, Hoedemaekers, Yvonne, Denjoy, Isabelle, Leenhardt, Antoine, Napolitano, Carlo, Shimizu, Wataru, Schott, Jean-Jacques, Gourraud, Jean-Baptiste, Makiyama, Takeru, Ohno, Seiko, Itoh, Hideki, Krahn, Andrew D., Antzelevitch, Charles, Roden, Dan M., Saenen, Johan, Borggrefe, Martin, Odening, Katja E., Ellinor, Patrick T., Tfelt-Hansen, Jacob, Skinner, Jonathan R., van den Berg, Maarten P., Olesen, Morten Salling, Brugada, Josep, Brugada, Ramón, Makita, Naomasa, Breckpot, Jeroen, Yoshinaga, Masao, Behr, Elijah R., Rydberg, Annika, Aiba, Takeshi, Kääb, Stefan, Priori, Silvia G., Guicheney, Pascale, Tan, Hanno L., Newton-Cheh, Christopher, Ackerman, Michael J., Schwartz, Peter J., Schulze-Bahr, Eric, Probst, Vincent, Horie, Minoru, Wilde, Arthur A., Tanck, Michael W.T., and Bezzina, Connie R.

Published
2020
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28. EN-452414-5 VENTRICULAR CONDUCTION IS A MARKER FOR ARRHYTHMIC RISK IN OVERLAP SODIUM CHANNEL DISEASE

Author

Wijeyeratne, Yanushi D., primary, Tanck, Michael, additional, Barc, Julien, additional, Muir, Alison, additional, Aiba, Takeshi, additional, Bos, Johan M., additional, Veltmann, Christian, additional, Galvin, Joseph M., additional, Crotti, Lia, additional, Ishikawa, Taisuke, additional, Ohno, Seiko, additional, Page, Stephen, additional, Denjoy, Isabelle, additional, Tester, David, additional, Muggenthaler, Martina, additional, Takahashi, Kazuhiro, additional, Raju, Hari, additional, GOURRAUD, JEAN BAPTISTE, additional, Redon, Richard, additional, Schott, Jean-Jacques, additional, Kyndt, Florence, additional, Haglund-Turnquist, Carla, additional, Pedrazzini, Matteo, additional, Torchio, Margherita, additional, Dagradi, Frederica, additional, Papadakis, Michael, additional, Sharma, Sanjay, additional, Petzer, Edward, additional, Roden, Dan M., additional, Horie, Minoru, additional, Schwartz, Peter J., additional, Makita, Naomasa, additional, Borggrefe, Martin M., additional, Ackerman, Michael J., additional, Shimizu, Wataru, additional, McKeown, Pascal, additional, PROBST, VINCENT, additional, and Behr, Elijah, additional

Published
2023
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29. Machine Learning–Based Phenogrouping in Mitral Valve Prolapse Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events

Author

Huttin, Olivier, primary, Girerd, Nicolas, additional, Jobbe-Duval, Antoine, additional, Constant Dit Beaufils, Anne-Laure, additional, Senage, Thomas, additional, Filippetti, Laura, additional, Cueff, Caroline, additional, Duarte, Kevin, additional, Fraix, Antoine, additional, Piriou, Nicolas, additional, Mandry, Damien, additional, Pace, Nathalie, additional, Le Scouarnec, Solena, additional, Capoulade, Romain, additional, Echivard, Matthieu, additional, Sellal, Jean Marc, additional, Marrec, Marie, additional, Beaumont, Marine, additional, Hossu, Gabriella, additional, Trochu, Jean-Noel, additional, Sadoul, Nicolas, additional, Marie, Pierre-Yves, additional, Guenancia, Charles, additional, Schott, Jean-Jacques, additional, Roussel, Jean-Christian, additional, Serfaty, Jean-Michel, additional, Selton-Suty, Christine, additional, and Le Tourneau, Thierry, additional

Published
2023
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30. Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis : a genome-wide study

Author

Yu Chen, Hao, Dina, Christian, Small, Aeron M., Shaffer, Christian M., Levinson, Rebecca T., Helgadóttir, Anna, Capoulade, Romain, Munter, Hans Markus, Martinsson, Andreas, Cairns, Benjamin J., Trudsø, Linea C., Hoekstra, Mary, Burr, Hannah A., Marsh, Thomas W., Damrauer, Scott M., Dufresne, Line, Le Scouarnec, Solena, Messika-Zeitoun, David, Ranatunga, Dilrini K., Whitmer, Rachel A., Bonnefond, Amélie, Sveinbjornsson, Garðar, Daníelsen, Ragnar, Arnar, David O., Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Gudbjartsson, Daníel F, Hólm, Hilma, Ghouse, Jonas, Olesen, Morten Salling, Christensen, Alex H., Mikkelsen, Susan, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, Erikstrup, Christian, Ostrowski, Sisse R., O'Donnell, Christopher J., Budoff, Matthew J., Gudnason, Vilmundur, Post, Wendy S., Rotter, Jerome I., Lathrop, Mark, Bundgaard, Henning, Johansson, Bengt, Ljungberg, Johan, Näslund, Ulf, Le Tourneau, Thierry, Smith, J Gustav, Wells, Quinn S., Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J., Clarke, Robert, Engert, James C., Thanassoulis, George, Yu Chen, Hao, Dina, Christian, Small, Aeron M., Shaffer, Christian M., Levinson, Rebecca T., Helgadóttir, Anna, Capoulade, Romain, Munter, Hans Markus, Martinsson, Andreas, Cairns, Benjamin J., Trudsø, Linea C., Hoekstra, Mary, Burr, Hannah A., Marsh, Thomas W., Damrauer, Scott M., Dufresne, Line, Le Scouarnec, Solena, Messika-Zeitoun, David, Ranatunga, Dilrini K., Whitmer, Rachel A., Bonnefond, Amélie, Sveinbjornsson, Garðar, Daníelsen, Ragnar, Arnar, David O., Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Gudbjartsson, Daníel F, Hólm, Hilma, Ghouse, Jonas, Olesen, Morten Salling, Christensen, Alex H., Mikkelsen, Susan, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, Erikstrup, Christian, Ostrowski, Sisse R., O'Donnell, Christopher J., Budoff, Matthew J., Gudnason, Vilmundur, Post, Wendy S., Rotter, Jerome I., Lathrop, Mark, Bundgaard, Henning, Johansson, Bengt, Ljungberg, Johan, Näslund, Ulf, Le Tourneau, Thierry, Smith, J Gustav, Wells, Quinn S., Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J., Clarke, Robert, Engert, James C., and Thanassoulis, George

Abstract

AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS: A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. CONCLUSION: Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

Published
2023
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31. Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis:a genome-wide study

Author

Wells, Quinn S, Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J, Clarke, Robert, Engert, James C, Thanassoulis, George, Wells, Quinn S, Söderberg, Stefan, Stefánsson, Kári, Schott, Jean-Jacques, Rader, Daniel J, Clarke, Robert, Engert, James C, and Thanassoulis, George

Abstract

Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies., Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

Published
2023

32. Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I

Author

Daumy, Xavier, Amarouch, Mohamed-Yassine, Lindenbaum, Pierre, Bonnaud, Stéphanie, Charpentier, Eric, Bianchi, Beatrice, Nafzger, Sabine, Baron, Estelle, Fouchard, Swanny, Thollet, Aurélie, Kyndt, Florence, Barc, Julien, Le Scouarnec, Solena, Makita, Naomasa, Le Marec, Hervé, Dina, Christian, Gourraud, Jean-Baptiste, Probst, Vincent, Abriel, Hugues, Redon, Richard, and Schott, Jean-Jacques

Published
2016
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33. GWAS Summary Statistics from a Global Meta-Analysis of Aortic Stenosis

Author

Chen, Hao Yu, PhD, Dina, Christian, PhD, Small, Aeron M., MD, Shaffer, Christian M., Levinson, Rebecca T., PhD, Helgadóttir, Anna, MD, PhD, Capoulade, Romain, PhD, Munter, Hans Markus, PhD, Martinsson, Andreas, MD, Cairns, Benjamin J., PhD, Trudsø, Linea C., Hoekstra, Mary, Burr, Hannah A., Marsh, Thomas W., Damrauer, Scott M., MD, Dufresne, Line, Scouarnec, Solena Le, PhD, Messika-Zeitoun, David, MD, PhD, Ranatunga, Dilrini K., Whitmer, Rachel A., PhD, Bonnefond, Amélie, PhD, Sveinbjornsson, Garðar, Daníelsen, Ragnar, MD, PhD, Arnar, David O., MD, PhD, Thorgeirsson, Gudmundur, MD, PhD, Thorsteinsdottir, Unnur, PhD, Gudbjartsson, Daníel F., PhD, Hólm, Hilma, MD, Ghouse, Jonas, MD, Olesen, Morten Salling, PhD, Christensen, Alex H., MD, Mikkelsen, Susan, MD, Jacobsen, Rikke Louise, Dowsett, Joseph, Pedersen, Ole Birger Vesterager, MD, Erikstrup, Christian, MD, Ostrowski, Sisse R., Regeneron Genetics Center, O'Donnell, Christopher J., MD, Budoff, Matthew J., MD, Gudnason, Vilmundur, MD, Post, Wendy S., MD, Rotter, Jerome I., MD, Lathrop, Mark, PhD, Bundgaard, Henning, Johansson, Bengt, MD, PhD, Ljungberg, Johan, MD, PhD, Näslund, Ulf, MD, PhD, Tourneau, Thierry Le, MD, PhD, Smith, J. Gustav, MD, Wells, Quinn S., MD, Söderberg, Stefan, MD, PhD, Stefánsson, Kári, MD, PhD, Schott, Jean-Jacques, PhD, Rader, Daniel J., MD, Clarke, Robert, MD, Engert, James C., PhD, and Thanassoulis, George

Abstract

GWAS Summary Statistics for a Global Meta-Analysis of Aortic Stenosis in the TARGET Consortium 10.5281/zenodo.7630002 This dataset contains the genome-wide association summary statistics for a Global Meta-Analysis of Aortic Stenosis. For the analysis description and included cohorts, please see Chen et al., the European Heart Journal (2023). The data are provided on an "AS-IS" basis, without warranty of any type, expressed or implied, including but not limited to any warranty as to their performance, merchantability, or fitness for any particular purpose. If investigators use these data, any and all consequences are entirely their responsibility. By downloading and using these data, you agree that you will cite the appropriate publication in any communications or publications arising directly or indirectly from these data. When using this data, please cite the paper and this repository: Chenet al., GWAS Summary Statistics for a Global Meta-Analysis of Aortic Stenosis,the European Heart Journal (2023). Zenodo.10.5281/zenodo.7630002 Column headers: CHR: Chromosome code. Not present with 'no-map' modifier. BP: Base-pair coordinate. Not present with 'no-map' modifier. SNP: Variant identifier A1: Effect Allele A2: Other Allele N_cohort: Number of valid studies for variant P: Fixed-effects meta-analysis p-value P.R.: Random-effects meta-analysis p-value OR: Fixed-effects BETA/OR estimate OR.R.:  Random-effects BETA/OR estimate Q: p-value for Cochran's Q statistic I: I2 heterogeneity index (0-100 scale) N_ind: Number of individuals Fundings: Fundings for this study were obtained from the following (listed in alphabetical order): ALFEDIAM Ardix Medical Assistance Publique - Hôpitaux de Paris Association Diabète Risque Vasculaire Bayer Diagnostics Becton Dickinson British Heart Foundation British Heart Foundation Oxford Centre Canadian Institutes for Health Research Capital Regions Research Council Cardionics, Merck Santé, Novo Nordisk CNAMTS, Lilly, Novartis Pharma Cohortes Santé TGIR County Council of Västerbotten Crafoord Foundation Ellison Medical Foundation European Research Council Fédération Française de Cardiologie Fédération Française de Cardiologie, a Fondation Coeur et Recherche Fonds de Recherche du Québec - Santé. French Regional Council of Pays-de-la-Loire (VaCaRMe program) Heart and Stroke Foundation of Canada Heart Foundation of Northern Sweden. Kaiser Permanente Knut and Alice Wallenberg foundation to the Wallenberg Center La Fondation de France Medical Research Council and the University of Oxford National Center for Advancing Translational Sciences (CTSI) National Heart, Lung, and Blood Institute (NHLBI) National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) National Institutes of Health Novo Nordisk Foundation ONIVINS Robert Wood Johnson Foundation Sanofi-Aventis; by INSERM (Réseaux en Santé Publique, Interactions entre les déterminants de la santé) Skåne University Hospital Société francophone du diabète Swedish Foundation for Strategic Research Swedish Heart–Lung Foundation Swedish National Health Service Swedish Research Council The Innovation Fund Denmark Umeå University U.S. Department of Veteran Affairs Vanderbilt University Medical Center’s institutional funding Wayne and Gladys Valley Foundation &nbsp

Published
2023
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34. Genetics and pathophysiology of mitral valve prolapse

Author

Delwarde, Constance, primary, Capoulade, Romain, additional, Mérot, Jean, additional, Le Scouarnec, Solena, additional, Bouatia-Naji, Nabila, additional, Yu, Mengyao, additional, Huttin, Olivier, additional, Selton-Suty, Christine, additional, Sellal, Jean-Marc, additional, Piriou, Nicolas, additional, Schott, Jean-Jacques, additional, Dina, Christian, additional, and Le Tourneau, Thierry, additional

Published
2023
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36. Variations in the poly-histidine repeat motif of HOXA1 contribute to bicuspid aortic valve in mouse and zebrafish

Author

Odelin, Gaelle, Faucherre, Adèle, Marchese, Damien, Pinard, Amélie, Jaouadi, Hager, Le Scouarnec, Solena, Deleuze, Jean-François, Génin, Emmanuelle, Lindenbaum, Pierre, Redon, Richard, Schott, Jean-Jacques, Chiarelli, Raphaël, Achouri, Younes, Faure, Emilie, Herbane, Marine, Théron, Alexis, Avierinos, Jean-François, Jopling, Chris, Collod-Béroud, Gwenaëlle, Rezsohazy, René, Zaffran, Stéphane, UCL - SST/LIBST - Louvain Institute of Biomolecular Science and Technology, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut du Thorax [Nantes], Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), 'Association Française contre les Myopathies' [NMH-Decrypt Project],the 'Fondation pour la Recherche Médicale'[DPC20111123002], the 'Institut National de la Santé et de laRecherche Médicale' and 'la Fondation Leducq' to S.Z. This workwas supported by the 'Fonds de la recherche Scientifique FNRS'[Crédit de recherche (CDR) J.0157.21] and the 'Fonds spéciaux derecherche' (FSR, UCLouvain) to R.R. A.P. received PhD fellowshipsfrom the 'Association Française du syndrome de Marfan et apparentés'.A.F. and C.J. are members of the Laboratory of ExcellenceIon Channel Science and Therapeutics supported by a grant fromthe ANR. Work in the C.J lab is supported by a grant from the 'laFondation Leducq', ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-LABX-0013,GENMED,Medical Genomics(2010), and ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011)

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Organogenesis, General Biochemistry, General Physics and Astronomy, Genetics and Molecular Biology, General Chemistry, Development, Heart development, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Bicuspid aortic valve (BAV), the most common cardiovascular malformation occurs in 0.5–1.2% of the population. Although highly heritable, few causal mutations have been identified in BAV patients. Here, we report the targeted sequencing of HOXA1 in a cohort of BAV patients and the identification of rare indel variants in the homopolymeric histidine tract of HOXA1. In vitro analysis shows that disruption of this motif leads to a significant reduction in protein half-life and defective transcriptional activity of HOXA1. In zebrafish, targeting hoxa1a ortholog results in aortic valve defects. In vivo assays indicates that these variants behave as dominant negatives leading abnormal valve development. In mice, deletion of Hoxa1 leads to BAV with a very small, rudimentary non-coronary leaflet. We also show that 17% of homozygous Hoxa1 −1His knock-in mice present similar phenotype. Genetic lineage tracing in Hoxa1 −/− mutant mice reveals an abnormal reduction of neural crest-derived cells in the valve leaflet, which is caused by a failure of early migration of these cells.

Published
2023
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41. Progressive Cardiac Conduction Disease

Author

Schott, Jean-Jacques, Charpentier, Flavien, Marec, Hervé Le, Gussak, Ihor, editor, Antzelevitch, Charles, editor, Wilde, Arthur A. M., editor, Friedman, Paul A., editor, Ackerman, Michael J., editor, and Shen, Win-Kuang, editor

Published
2008
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42. Multimodality imaging and transcriptomics to phenotype mitral valve dystrophy in a unique knock-in Filamin-Arat model

Author

Delwarde, Constance, primary, Toquet, Claire, additional, Aumond, Pascal, additional, Kayvanjoo, Amir Hossein, additional, Foucal, Adrien, additional, Le Vely, Benjamin, additional, Baudic, Manon, additional, Lauzier, Benjamin, additional, Blandin, Stéphanie, additional, Véziers, Joëlle, additional, Paul-Gilloteaux, Perrine, additional, Lecointe, Simon, additional, Baron, Estelle, additional, Massaiu, Ilaria, additional, Poggio, Paolo, additional, Rémy, Séverine, additional, Anegon, Ignacio, additional, Le Marec, Hervé, additional, Monassier, Laurent, additional, Schott, Jean Jacques, additional, Mass, Elvira, additional, Barc, Julien, additional, Le Tourneau, Thierry, additional, Merot, Jean, additional, and Capoulade, Romain, additional

Published
2022
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43. Burden of rare variants in arrhythmogenic cardiomyopathy with right dominant form‐associated genes provides new insights for molecular diagnosis and clinical management

Author

Goudal, Adeline, primary, Karakachoff, Matilde, additional, Lindenbaum, Pierre, additional, Baron, Estelle, additional, Bonnaud, Stéphanie, additional, Kyndt, Florence, additional, Arnaud, Marine, additional, Minois, Damien, additional, Bourcereau, Emmanuelle, additional, Thollet, Aurélie, additional, Deleuze, Jean‐François, additional, Genin, Emmanuelle, additional, Wiart, François, additional, Pasquié, Jean‐Luc, additional, Galand, Vincent, additional, Sacher, Frédéric, additional, Dina, Christian, additional, Redon, Richard, additional, Bezieau, Stéphane, additional, Schott, Jean‐Jacques, additional, Probst, Vincent, additional, and Barc, Julien, additional

Published
2022
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45. Mitral valve disease—morphology and mechanisms

Author

Levine, Robert A., Hagége, Albert A., Judge, Daniel P., Padala, Muralidhar, Dal-Bianco, Jacob P., Aikawa, Elena, Beaudoin, Jonathan, Bischoff, Joyce, Bouatia-Naji, Nabila, Bruneval, Patrick, Butcher, Jonathan T., Carpentier, Alain, Chaput, Miguel, Chester, Adrian H., Clusel, Catherine, Delling, Francesca N., Dietz, Harry C., Dina, Christian, Durst, Ronen, Fernandez-Friera, Leticia, Handschumacher, Mark D., Jensen, Morten O., Jeunemaitre, Xavier P., Marec, Hervé Le, Tourneau, Thierry Le, Markwald, Roger R., Mérot, Jean, Messas, Emmanuel, Milan, David P., Neri, Tui, Norris, Russell A., Peal, David, Perrocheau, Maelle, Probst, Vincent, Pucéat, Michael, Rosenthal, Nadia, Solis, Jorge, Schott, Jean-Jacques, Schwammenthal, Ehud, Slaugenhaupt, Susan A., Song, Jae-Kwan, and Yacoub, Magdi H.

Published
2015
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46. Non-coding deletion induces 3D chromatin remodelling and PITX2 expression dysregulation associated with a new syndromic cardiac disorder

Author

Baudic, Manon, primary, Murata, Hiroshigue, additional, Bosada, Fernanda, additional, Melo, Uirá Souto, additional, Ishikawa, Taisuke, additional, Aizawa, Takanori, additional, Guedon, Amaury, additional, Baron, Estelle, additional, Foucal, Adrien, additional, Lindenbaum, Pierre, additional, Le Scouarnec, Solena, additional, Makita, Naomasa, additional, Le Marec, Hervé, additional, Vieyres, Claude, additional, Mundlos, Stephan, additional, Christoffels, Vincent M., additional, Makiyama, Takeru, additional, Probst, Vincent, additional, Schott, Jean-Jacques, additional, and Barc, Julien, additional

Published
2022
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47. Mitral Valve Dystrophy: What role do leukocytes play?

Author

Delwarde, Constance, primary, Le Vély, Benjamin, additional, Kayvanjoo, Amir H., additional, Aumond, Pascal, additional, Remy, Séverine, additional, Monassier, Laurent, additional, Toquet, Claire, additional, Schott, Jean-Jacques, additional, Le Tourneau, Thierry, additional, Mass, Elvira, additional, Mérot, Jean, additional, and Capoulade, Romain, additional

Published
2022
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48. Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study

Author

Tortigue, Marine, primary, Nield, Lynne E., additional, Karakachoff, Matilde, additional, McLeod, Christopher J., additional, Belli, Emre, additional, Babu-Narayan, Sonya V., additional, Prigent, Solène, additional, Boet, Angèle, additional, Conway, Miriam, additional, Elder, Robert W., additional, Ladouceur, Magalie, additional, Khairy, Paul, additional, Kowalik, Ewa, additional, Kalfa, David M., additional, Barron, David J., additional, Mussa, Shafi, additional, Hiippala, Anita, additional, Temple, Joel, additional, Abadir, Sylvia, additional, Le Gloan, Laurianne, additional, Lachaud, Matthias, additional, Sanatani, Shubhayan, additional, Thambo, Jean-Benoit, additional, Gronier, Céline Grunenwald, additional, Amedro, Pascal, additional, Vaksmann, Guy, additional, Charbonneau, Anne, additional, Koutbi, Linda, additional, Ovaert, Caroline, additional, Houeijeh, Ali, additional, Combes, Nicolas, additional, Maury, Philippe, additional, Duthoit, Guillaume, additional, Hiel, Bérengère, additional, Erickson, Christopher C., additional, Bonnet, Caroline, additional, Van Hare, George F., additional, Dina, Christian, additional, Karsenty, Clément, additional, Fournier, Emmanuelle, additional, Le Bloa, Mathieu, additional, Pass, Robert H., additional, Liberman, Leonardo, additional, Happonen, Juha-Matti, additional, Perry, James C., additional, Romefort, Bénédicte, additional, Benbrik, Nadir, additional, Hauet, Quentin, additional, Fraisse, Alain, additional, Gatzoulis, Michael A., additional, Abrams, Dominic J., additional, Dubin, Anne M., additional, Ho, Siew Yen, additional, Redon, Richard, additional, Bacha, Emile A., additional, Schott, Jean-Jacques, additional, and Baruteau, Alban-Elouen, additional

Published
2022
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49. BS-515-01 NON-CODING DELETION INDUCES 3D CHROMATIN REMODELLING AND PITX2 EXPRESSION DYSREGULATION ASSOCIATED WITH A SYNDROMIC CARDIAC DISORDER

Author

Baudic, Manon, primary, Murata, Hiroshige, additional, Bosada, Fernanda M., additional, Melo, Uira Souto, additional, Ishikawa, Taisuke, additional, Aizawa, Takanori, additional, Guedon, Amaury, additional, Baron, Estelle, additional, FOUCAL, ADRIEN, additional, Lindenbaum, Pierre, additional, Le Scouarnec, Solena, additional, Shimizu, Wataru, additional, GOURRAUD, JEAN BAPTISTE, additional, Makita, Naomasa, additional, Le Marec, Herve, additional, Vieyres, Claude, additional, Mundlos, Stephan, additional, Christoffels, Vincent M., additional, Makiyama, Takeru, additional, PROBST, VINCENT, additional, Schott, Jean-Jacques, additional, and Barc, Julien, additional

Published
2022
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50. BS-513-02 GENOME-WIDE ASSOCIATION ANALYSES IDENTIFY NOVEL BRUGADA SYNDROME RISK LOCI AND HIGHLIGHT A NEW MECHANISM OF SODIUM CHANNEL REGULATION IN DISEASE SUSCEPTIBILITY

Author

Barc, Julien, primary, Tadros, Rafik, additional, Glinge, Charlotte, additional, Chiang, David Y., additional, jouni, Mariam, additional, Simonet, Floriane, additional, Tanck, Michael, additional, George, Alfred L., additional, MacRae, Calum A., additional, Burridge, Paul, additional, Dina, Christian, additional, Probst, Vincent, additional, Wilde, Arthur A.M., additional, Schott, Jean-Jacques, additional, Redon, Richard, additional, and Bezzina, Connie R., additional

Published
2022
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