Author: "Pier, D." / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

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54 results on '"Pier, D."'

1. Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies

Author: Onderzoek Precision medicine, Kukendrarajah, Kishore, Farmaki, Aliki Eleni, Lambiase, Pier D., Schilling, Richard, Finan, Chris, Floriaan Schmidt, Amand, Providencia, Rui, Onderzoek Precision medicine, Kukendrarajah, Kishore, Farmaki, Aliki Eleni, Lambiase, Pier D., Schilling, Richard, Finan, Chris, Floriaan Schmidt, Amand, and Providencia, Rui
Published: 2024

2. Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Author: Sheppard, S.E., Bryant, L., Wickramasekara, R.N., Vaccaro, C., Robertson, B., Hallgren, J., Hulen, J., Watson, C.J., Faundes, V., Duffourd, Y., Lee, P., Simon, M.C., Cruz, X. de la, Padilla, N., Flores-Mendez, M., Akizu, N., Smiler, J., Pellegrino Da Silva, R., Li, D., March, M., Diaz-Rosado, A., Peixoto de Barcelos, I., Choa, Z.X., Lim, C.Y., Dubourg, C., Journel, H., Demurger, F., Mulhern, M., Akman, C., Lippa, N., Andrews, M., Baldridge, D., Constantino, J., Haeringen, A. van, Snoeck-Streef, I., Chow, P., Hing, A., Graham Jr, J.M., Au, M., Faivre, L., Shen, W., Mao, R., Palumbos, J., Viskochil, D., Gahl, W., Tifft, C., Macnamara, E., Hauser, N., Miller, R., Maffeo, J., Afenjar, A., Doummar, D., Keren, B., Arn, P., Macklin-Mantia, S., Meerschaut, I., Callewaert, B., Reis, A., Zweier, C., Brewer, C., Saggar, A., Smeland, M.F., Kumar, Ajith, Elmslie, F., Deshpande, C., Nizon, M., Cogne, B., Ierland, Y. van, Wilke, M., Slegtenhorst, M. van, Koudijs, S., Chen, J.Y., Dredge, D., Pier, D., Wortmann, S.B., Kamsteeg, E.J., Koch, J., Haynes, D., Pollack, L., Titheradge, H., Ranguin, K., Denommé-Pichon, A.S., Weber, S., Perez de la Fuente, R., Sanchez Del Pozo, J., Lezana Rosales, J.M., Joset, P., Steindl, K., Rauch, A., Mei, D., Mari, F., Guerrini, R., Lespinasse, J., Tran Mau-Them, F., Philippe, C., Dauriat, B., Raymond, L., Moutton, S., Cueto-González, A.M., Tan, T.Y., Mignot, C., Grotto, S., Renaldo, F., Drivas, T.G., Hennessy, L., Raper, A., Parenti, I., Kaiser, F.J., Kuechler, A., Busk, Ø.L., Islam, L., Siedlik, J.A., Henderson, L.B., Juusola, J., Person, R., Schnur, R.E., Vitobello, A., Banka, S., Bhoj, E.J., Stessman, H.A.F., Sheppard, S.E., Bryant, L., Wickramasekara, R.N., Vaccaro, C., Robertson, B., Hallgren, J., Hulen, J., Watson, C.J., Faundes, V., Duffourd, Y., Lee, P., Simon, M.C., Cruz, X. de la, Padilla, N., Flores-Mendez, M., Akizu, N., Smiler, J., Pellegrino Da Silva, R., Li, D., March, M., Diaz-Rosado, A., Peixoto de Barcelos, I., Choa, Z.X., Lim, C.Y., Dubourg, C., Journel, H., Demurger, F., Mulhern, M., Akman, C., Lippa, N., Andrews, M., Baldridge, D., Constantino, J., Haeringen, A. van, Snoeck-Streef, I., Chow, P., Hing, A., Graham Jr, J.M., Au, M., Faivre, L., Shen, W., Mao, R., Palumbos, J., Viskochil, D., Gahl, W., Tifft, C., Macnamara, E., Hauser, N., Miller, R., Maffeo, J., Afenjar, A., Doummar, D., Keren, B., Arn, P., Macklin-Mantia, S., Meerschaut, I., Callewaert, B., Reis, A., Zweier, C., Brewer, C., Saggar, A., Smeland, M.F., Kumar, Ajith, Elmslie, F., Deshpande, C., Nizon, M., Cogne, B., Ierland, Y. van, Wilke, M., Slegtenhorst, M. van, Koudijs, S., Chen, J.Y., Dredge, D., Pier, D., Wortmann, S.B., Kamsteeg, E.J., Koch, J., Haynes, D., Pollack, L., Titheradge, H., Ranguin, K., Denommé-Pichon, A.S., Weber, S., Perez de la Fuente, R., Sanchez Del Pozo, J., Lezana Rosales, J.M., Joset, P., Steindl, K., Rauch, A., Mei, D., Mari, F., Guerrini, R., Lespinasse, J., Tran Mau-Them, F., Philippe, C., Dauriat, B., Raymond, L., Moutton, S., Cueto-González, A.M., Tan, T.Y., Mignot, C., Grotto, S., Renaldo, F., Drivas, T.G., Hennessy, L., Raper, A., Parenti, I., Kaiser, F.J., Kuechler, A., Busk, Ø.L., Islam, L., Siedlik, J.A., Henderson, L.B., Juusola, J., Person, R., Schnur, R.E., Vitobello, A., Banka, S., Bhoj, E.J., and Stessman, H.A.F.
Abstract: Item does not contain fulltext, Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems.
Published: 2023

3. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.

Author: Young, William J, Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D, Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, Munroe, Patricia B, Young, William J, Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D, Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, and Munroe, Patricia B
Abstract: The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
Published: 2023

4. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Author: Young, William J., Haessler, Jeffrey, Benjamins, Jan Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R., Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R., Concas, Maria Pina, Duong, Thuy Vy, Foco, Luisa, Isaksen, Jonas L., Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L., Sitlani, Colleen M., Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A., Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Jackson, Rebecca D., Kors, Jan A., Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W., Morrison, Alanna C., Navarro, Pau, Porteous, David J., Pramstaller, Peter P., Reiner, Alexander P., Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z., Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R., Whitsel, Eric A., Wiggins, Kerri L., Arking, Dan E., Avery, Christy L., Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J. Wouter, Mook-Kanamori, Dennis O., Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M., Pattaro, Cristian, Ribeiro, Antonio Luiz P., Rotter, Jerome I., Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James G., Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J., Wilson, James F., Kanters, Jørgen K., Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D., Tereshchenko, Larisa G., Munroe, Patricia B., Young, William J., Haessler, Jeffrey, Benjamins, Jan Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R., Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R., Concas, Maria Pina, Duong, Thuy Vy, Foco, Luisa, Isaksen, Jonas L., Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L., Sitlani, Colleen M., Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A., Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Jackson, Rebecca D., Kors, Jan A., Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W., Morrison, Alanna C., Navarro, Pau, Porteous, David J., Pramstaller, Peter P., Reiner, Alexander P., Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z., Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R., Whitsel, Eric A., Wiggins, Kerri L., Arking, Dan E., Avery, Christy L., Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J. Wouter, Mook-Kanamori, Dennis O., Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M., Pattaro, Cristian, Ribeiro, Antonio Luiz P., Rotter, Jerome I., Stricker, Bruno H., van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James G., Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J., Wilson, James F., Kanters, Jørgen K., Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D., Tereshchenko, Larisa G., and Munroe, Patricia B.
Abstract: The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
Published: 2023

5. Circadian and Seasonal Pattern of Arrhythmic Events in Arrhythmogenic Cardiomyopathy Patients

Author: Castelletti, S, Orini, M, Vischer, A, Mckenna, W, Lambiase, P, Pantazis, A, Crotti, L, Castelletti, Silvia, Orini, Michele, Vischer, Annina S, McKenna, William J, Lambiase, Pier D, Pantazis, Antonios, Crotti, Lia, Castelletti, S, Orini, M, Vischer, A, Mckenna, W, Lambiase, P, Pantazis, A, Crotti, L, Castelletti, Silvia, Orini, Michele, Vischer, Annina S, McKenna, William J, Lambiase, Pier D, Pantazis, Antonios, and Crotti, Lia
Abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease associated with an increased risk of life-threatening arrhythmias. The aim of the present study was to evaluate the association of ventricular arrhythmias (VA) with circadian and seasonal variation in ARVC. One hundred two ARVC patients with an implantable cardioverter defibrillator (ICD) were enrolled in the study. Arrhythmic events included (a) any initial ventricular tachycardia (VT) or fibrillation (VF) prompting ICD implantation, (b) any VT or non-sustained VT (NSVT) recorded by the ICD, and (c) appropriate ICD shocks/therapy. Differences in the annual incidence of events across seasons (winter, spring, summer, autumn) and period of the day (night, morning, afternoon, evening) were assessed both for all cardiac events and major arrhythmic events. In total, 67 events prior to implantation and 263 ICD events were recorded. These included 135 major (58 ICD therapies, 57 self-terminating VT, 20 sustained VT) and 148 minor (NSVT) events. A significant increase in the frequency of events was observed in the afternoon versus in the nights and mornings (p = 0.016). The lowest number of events was registered in the summer, with a peak in the winter (p < 0.001). Results were also confirmed when excluding NSVT. Arrhythmic events in ARVC follow a seasonal variation and a circadian rhythm. They are more prevalent in the late afternoon, the most active period of the day, and in the winter, supporting the role of physical activity and inflammation as triggers of events.
Published: 2023

6. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Author: Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D., Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, Munroe, Patricia B, Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D., Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, and Munroe, Patricia B
Abstract: The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
Published: 2023

7. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Author: Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D., Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, Munroe, Patricia B, Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D., Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, and Munroe, Patricia B
Abstract: The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
Published: 2023

8. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Author: RWE/Causal inference, Child Health, Gezonde Vaten, Circulatory Health, Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D, Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, Munroe, Patricia B, RWE/Causal inference, Child Health, Gezonde Vaten, Circulatory Health, Young, William J, Haessler, Jeffrey, Benjamins, Jan-Walter, Repetto, Linda, Yao, Jie, Isaacs, Aaron, Harper, Andrew R, Ramirez, Julia, Garnier, Sophie, van Duijvenboden, Stefan, Baldassari, Antoine R, Concas, Maria Pina, Duong, ThuyVy, Foco, Luisa, Isaksen, Jonas L, Mei, Hao, Noordam, Raymond, Nursyifa, Casia, Richmond, Anne, Santolalla, Meddly L, Sitlani, Colleen M, Soroush, Negin, Thériault, Sébastien, Trompet, Stella, Aeschbacher, Stefanie, Ahmadizar, Fariba, Alonso, Alvaro, Brody, Jennifer A, Campbell, Archie, Correa, Adolfo, Darbar, Dawood, De Luca, Antonio, Deleuze, Jean-François, Ellervik, Christina, Fuchsberger, Christian, Goel, Anuj, Grace, Christopher, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Jackson, Rebecca D, Kors, Jan A, Lima-Costa, Maria Fernanda, Linneberg, Allan, Macfarlane, Peter W, Morrison, Alanna C, Navarro, Pau, Porteous, David J, Pramstaller, Peter P, Reiner, Alexander P, Risch, Lorenz, Schotten, Ulrich, Shen, Xia, Sinagra, Gianfranco, Soliman, Elsayed Z, Stoll, Monika, Tarazona-Santos, Eduardo, Tinker, Andrew, Trajanoska, Katerina, Villard, Eric, Warren, Helen R, Whitsel, Eric A, Wiggins, Kerri L, Arking, Dan E, Avery, Christy L, Conen, David, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jukema, J Wouter, Mook-Kanamori, Dennis O, Olesen, Morten Salling, Padmanabhan, Sandosh, Psaty, Bruce M, Pattaro, Cristian, Ribeiro, Antonio Luiz P, Rotter, Jerome I, Stricker, Bruno H, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James G, Orini, Michele, Charron, Philippe, Watkins, Hugh, Kooperberg, Charles, Lin, Henry J, Wilson, James F, Kanters, Jørgen K, Sotoodehnia, Nona, Mifsud, Borbala, Lambiase, Pier D, Tereshchenko, Larisa G, and Munroe, Patricia B
Published: 2023

9. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

10. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
Full Text: View/download PDF

11. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
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12. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
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13. ECG T‐wave morphologic variations predict ventricular arrhythmic risk in low‐ and moderate‐risk populations

Author: Ramírez, J. (Julia), Kiviniemi, A. (Antti), van Duijvenboden, S. (Stefan), Tinker, A. (Andrew), Lambiase, P. D. (Pier D.), Junttila, J. (Juhani), Perkiömäki, J. S. (Juha S.), Huikuri, H. V. (Heikki V.), Orini, M. (Michele), Munroe, P. B. (Patricia B.), Ramírez, J. (Julia), Kiviniemi, A. (Antti), van Duijvenboden, S. (Stefan), Tinker, A. (Andrew), Lambiase, P. D. (Pier D.), Junttila, J. (Juhani), Perkiömäki, J. S. (Juha S.), Huikuri, H. V. (Heikki V.), Orini, M. (Michele), and Munroe, P. B. (Patricia B.)
Abstract: Background: Early identification of individuals at risk of sudden cardiac death (SCD) remains a major challenge. The ECG is a simple, common test, with potential for large‐scale application. We developed and tested the predictive value of a novel index quantifying T‐wave morphologic variations with respect to a normal reference (TMV), which only requires one beat and a single‐lead ECG. Methods and results: We obtained reference T‐wave morphologies from 23 962 participants in the UK Biobank study. With Cox models, we determined the association between TMV and life‐threatening ventricular arrhythmia in an independent data set from UK Biobank study without a history of cardiovascular events (N=51 794; median follow‐up of 122 months) and SCD in patients with coronary artery disease from ARTEMIS (N=1872; median follow‐up of 60 months). In UK Biobank study, 220 (0.4%) individuals developed life‐threatening ventricular arrhythmias. TMV was significantly associated with life‐threatening ventricular arrhythmias (hazard ratio [HR] of 1.13 per SD increase [95% CI, 1.03–1.24]; P=0.009). In ARTEMIS, 34 (1.8%) individuals reached the primary end point. Patients with TMV ≥5 had an HR for SCD of 2.86 (95% CI, 1.40–5.84; P=0.004) with respect to those with TMV <5, independently from QRS duration, corrected QT interval, and left ventricular ejection fraction. TMV was not significantly associated with death from a cause other than SCD. Conclusions: TMV identifies individuals at life‐threatening ventricular arrhythmia and SCD risk using a single‐beat single‐lead ECG, enabling inexpensive, quick, and safe risk assessment in large populations.
Published: 2022

14. Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology.

Author: de Groot, Natasja M S, Shah, Dipen, Boyle, Patrick M, Anter, Elad, Clifford, Gari D, Deisenhofer, Isabel, Deneke, Thomas, van Dessel, Pascal, Doessel, Olaf, Dilaveris, Polychronis, Heinzel, Frank R, Kapa, Suraj, Lambiase, Pier D, Lumens, Joost, Platonov, Pyotr G, Ngarmukos, Tachapong, Martinez, Juan Pablo, Sanchez, Alejandro Olaya, Takahashi, Yoshihide, Valdigem, Bruno Pereira, van der Veen, Alle Jan, Vernooy, Kevin, Casado Arroyo, Ruben, ESC Scientific Document Group, De Potter, Tom, Dinov, Borislav, Kosiuk, Jedrzej, Linz, Dominik, Neubeck, Lis, Svennberg, Emma, Kim, Young Hoon, Wan, Elaine, Lopez-Cabanillas, Nestor, Locati, Emanuela T, Macfarlane, Peter, de Groot, Natasja M S, Shah, Dipen, Boyle, Patrick M, Anter, Elad, Clifford, Gari D, Deisenhofer, Isabel, Deneke, Thomas, van Dessel, Pascal, Doessel, Olaf, Dilaveris, Polychronis, Heinzel, Frank R, Kapa, Suraj, Lambiase, Pier D, Lumens, Joost, Platonov, Pyotr G, Ngarmukos, Tachapong, Martinez, Juan Pablo, Sanchez, Alejandro Olaya, Takahashi, Yoshihide, Valdigem, Bruno Pereira, van der Veen, Alle Jan, Vernooy, Kevin, Casado Arroyo, Ruben, ESC Scientific Document Group, De Potter, Tom, Dinov, Borislav, Kosiuk, Jedrzej, Linz, Dominik, Neubeck, Lis, Svennberg, Emma, Kim, Young Hoon, Wan, Elaine, Lopez-Cabanillas, Nestor, Locati, Emanuela T, and Macfarlane, Peter
Abstract: We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near futu, info:eu-repo/semantics/published
Published: 2022

15. Subcutaneous implantable cardioverter-defibrillators:long-term results of the EFFORTLESS study

Author: Lambiase, Pier D., Theuns, Dominic A., Murgatroyd, Francis, Barr, Craig, Eckardt, Lars, Neuzil, Petr, Scholten, Marcoen, Hood, Margaret, Kuschyk, Jȕrgen, Brisben, Amy J., Carter, Nathan, Stivland, Timothy M., Knops, Reinoud, Boersma, Lucas V.A., Lambiase, Pier D., Theuns, Dominic A., Murgatroyd, Francis, Barr, Craig, Eckardt, Lars, Neuzil, Petr, Scholten, Marcoen, Hood, Margaret, Kuschyk, Jȕrgen, Brisben, Amy J., Carter, Nathan, Stivland, Timothy M., Knops, Reinoud, and Boersma, Lucas V.A.
Abstract: AIMS: To report 5-year outcomes of EFFORTLESS registry patients with early generation subcutaneous implantable cardioverter-defibrillator (S-ICD) devices. METHODS AND RESULTS: Kaplan-Meier, trend and multivariable analyses were performed for mortality and late (years 2-5) complications, appropriate shock (AS) and inappropriate shock (IAS) rates. Nine hundred and eighty-four of 994 enrolled patients with diverse diagnoses (28% female, 48 ± 17 years, body mass index 27 ± 6 kg/m2, ejection fraction 43 ± 18%) underwent S-ICD implantation. Median follow-up was 5.1 years (interquartile range 4.7-5.5 years). All-cause mortality was 9.3% (95% confidence interval 7.2-11.3%) at 5 years; 703 patients remained in follow-up on study completion, 171 withdrew including 87 (8.8%) with device explanted, and 65 (6.6%) lost to follow-up. Of the explants, only 20 (2.0%) patients needed a transvenous device for pacing indications. First and final shock efficacy for discrete ventricular arrhythmias was consistent at 90% and 98%, respectively, with storm episode final shock efficacy at 95.2%. Time to therapy remained unaltered. Overall 1- and 5-year complication rates were 8.9% and 15.2%, respectively. Early complications did not predict later complications. There were no structural lead failures. Inappropriate shock rates at 1 and 5 years were 8.7% and 16.9%, respectively. Self-terminating inappropriately sensed episodes predicted late IAS. Predictors of late AS included self-terminating appropriately sensed episodes and earlier AS. CONCLUSION: In this diverse S-ICD registry population, spontaneous shock efficacy was consistently high over 5 years. Very few patients underwent S-ICD replacement with a transvenous device for pacing indications. Treated and self-terminating arrhythmic episodes predict future shock events, which should encourage more personalized device optimization.
Published: 2022

16. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan Walter, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J.F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan Walter, Haessler, Jeffrey, Lyytikäinen, Leo Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki V., Hutri-Kähönen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo Riitta, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J.F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome I., Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022

17. Author Correction: Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility (Nature Genetics, (2022), 54, 3, (232-239), 10.1038/s41588-021-01007-6)

Author: Julien Barc, Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, Connie R. Bezzina, Julien Barc, Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, and Connie R. Bezzina
Abstract: In the version of this article initially published, Federico Manevy’s name appeared with a middle initial in error. The name has been corrected in the HTML and PDF versions of the article.
Published: 2022

18. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B., Young, William J., Lahrouchi, Najim, Isaacs, Aaron, Duong, Thuy Vy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A., Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikainen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E., Weiss, Stefan, Baldassari, Antoine R., Bartz, Traci M., Cook, James P., Evans, Daniel S., Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L., Lin, Honghuang, Mei, Hao, Moscati, Arden, Mueller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A., Tarazona-Santos, Eduardo, Theriault, Sebastien, van Duijvenboden, Stefan, Warren, Helen R., Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C., Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J., Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T., Felix, Stephan B., Froguel, Philippe, Fuchsberger, Christian, Gogele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R., Huang, Paul L., Huikuri, Heikki, V, Hutri-Kahonen, Nina, Ikram, M. Arfan, Jackson, Rebecca D., Junttila, Juhani, Kavousi, Maryam, Kors, Jan A., Leal, Thiago P., Lemaitre, Rozenn N., Lin, Henry J., Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W., Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P., Mitchell, Rebecca N., Mononen, Nina, Montasser, May E., Morrison, Alanna C., Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K., Pelliccione, Giulia, Pittman, Alan, Porteous, David J., Pramstaller, Peter P., Preuss, Michael H., Raitakari, Olli T., Reiner, Alexander P., Ribeiro, Antonio Luiz P., Rice, Kenneth M., Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M. Benjamin, Sinagra, Gianfranco, Sinner, Moritz F., Soliman, Elsayed Z., Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D., Tinker, Andrew, Trompet, Stella, Uitterlinden, Andre, Voelker, Uwe, Voelzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A., Wilson, James G., Avery, Christy L., Conen, David, Correa, Adolfo, Cucca, Francesco, Dorr, Marcus, Gharib, Sina A., Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Kaab, Stefan, Kahonen, Mika, Kanters, Jorgen K., Kooperberg, Charles, Lehtimaki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J. F., Lubitz, Steven A., Mook-Kanamori, Dennis O., Morris, Andrew P., O'Connell, Jeffrey R., Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M., Rotter, Jerome, I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M., Verweij, Niek, Wilson, James F., Arking, Dan E., Ramirez, Julia, Lambiase, Pier D., Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B.
Abstract: The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2022
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19. Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Author: Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, Connie R. Bezzina, Barc, J, Tadros, R, Glinge, C, Chiang, D, Jouni, M, Simonet, F, Jurgens, S, Baudic, M, Nicastro, M, Potet, F, Offerhaus, J, Walsh, R, Hoan Choi, S, Verkerk, A, Mizusawa, Y, Anys, S, Minois, D, Arnaud, M, Duchateau, J, Wijeyeratne, Y, Muir, A, Papadakis, M, Castelletti, S, Torchio, M, Gil Ortuño, C, Lacunza, J, Giachino, D, Cerrato, N, Martins, R, Campuzano, O, Van Dooren, S, Thollet, A, Kyndt, F, Mazzanti, A, Clémenty, N, Bisson, A, Corveleyn, A, Stallmeyer, B, Dittmann, S, Saenen, J, Noël, A, Honarbakhsh, S, Rudic, B, Marzak, H, Rowe, M, Federspiel, C, Le Page, S, Placide, L, Milhem, A, Barajas-Martinez, H, Beckmann, B, Krapels, I, Steinfurt, J, Gregers Winkel, B, Jabbari, R, Shoemaker, M, Boukens, B, Škorić-Milosavljević, D, Bikker, H, Manevy, F, Lichtner, P, Ribasés, M, Meitinger, T, Müller-Nurasyid, M, Group, K, Veldink, J, van den Berg, L, Van Damme, P, Cusi, D, Lanzani, C, Rigade, S, Charpentier, E, Baron, E, Bonnaud, S, Lecointe, S, Donnart, A, Le Marec, H, Chatel, S, Karakachoff, M, Bézieau, S, London, B, Tfelt-Hansen, J, Roden, D, Odening, K, Cerrone, M, Chinitz, L, Volders, P, van de Berg, M, Laurent, G, Faivre, L, Antzelevitch, C, Kääb, S, Al Arnaout, A, Dupuis, J, Pasquie, J, Billon, O, Roberts, J, Jesel, L, Borggrefe, M, Lambiase, P, Mansourati, J, Loeys, B, Leenhardt, A, Guicheney, P, Maury, P, Schulze-Bahr, E, Robyns, T, Breckpot, J, Babuty, D, Priori, S, Napolitano, C, Referral Center for inherited cardiac arrhythmia, N, de Asmundis, C, Brugada, P, Brugada, R, Arbelo, E, Brugada, J, Mabo, P, Behar, N, Giustetto, C, Sabater Molina, M, Gimeno, J, Hasdemir, C, Schwartz, P, Crotti, L, Mckeown, P, Sharma, S, Behr, E, Haissaguerre, M, Sacher, F, Rooryck, C, Tan, H, Remme, C, Postema, P, Delmar, M, Ellinor, P, Lubitz, S, Gourraud, J, Tanck, M, L. George Jr., A, Macrae, C, Burridge, P, Dina, C, Probst, V, Wilde, A, Schott, J, Redon &amp, R, Bezzina, C, Julien Barc, Rafik Tadros, Charlotte Glinge, David Y. Chiang, Mariam Jouni, Floriane Simonet, Sean J. Jurgens, Manon Baudic, Michele Nicastro, Franck Potet, Joost A. Offerhaus, Roddy Walsh, Seung Hoan Choi, Arie O. Verkerk, Yuka Mizusawa, Soraya Anys, Damien Minois, Marine Arnaud, Josselin Duchateau, Yanushi D. Wijeyeratne, Alison Muir, Michael Papadakis, Silvia Castelletti, Margherita Torchio, Cristina Gil Ortuño, Javier Lacunza, Daniela F. Giachino, Natascia Cerrato, Raphaël P. Martins, Oscar Campuzano, Sonia Van Dooren, Aurélie Thollet, Florence Kyndt, Andrea Mazzanti, Nicolas Clémenty, Arnaud Bisson, Anniek Corveleyn, Birgit Stallmeyer, Sven Dittmann, Johan Saenen, Antoine Noël, Shohreh Honarbakhsh, Boris Rudic, Halim Marzak, Matthew K. Rowe, Claire Federspiel, Sophie Le Page, Leslie Placide, Antoine Milhem, Hector Barajas-Martinez, Britt-Maria Beckmann, Ingrid P. Krapels, Johannes Steinfurt, Bo Gregers Winkel, Reza Jabbari, Moore B. Shoemaker, Bas J. Boukens, Doris Škorić-Milosavljević, Hennie Bikker, Federico Manevy, Peter Lichtner, Marta Ribasés, Thomas Meitinger, Martina Müller-Nurasyid, KORA-Study Group, Jan H. Veldink, Leonard H. van den Berg, Philip Van Damme, Daniele Cusi, Chiara Lanzani, Sidwell Rigade, Eric Charpentier, Estelle Baron, Stéphanie Bonnaud, Simon Lecointe, Audrey Donnart, Hervé Le Marec, Stéphanie Chatel, Matilde Karakachoff, Stéphane Bézieau, Barry London, Jacob Tfelt-Hansen, Dan Roden, Katja E. Odening, Marina Cerrone, Larry A. Chinitz, Paul G. Volders, Maarten P. van de Berg, Gabriel Laurent, Laurence Faivre, Charles Antzelevitch, Stefan Kääb, Alain Al Arnaout, Jean-Marc Dupuis, Jean-Luc Pasquie, Olivier Billon, Jason D. Roberts, Laurence Jesel, Martin Borggrefe, Pier D. Lambiase, Jacques Mansourati, Bart Loeys, Antoine Leenhardt, Pascale Guicheney, Philippe Maury, Eric Schulze-Bahr, Tomas Robyns, Jeroen Breckpot, Dominique Babuty, Silvia G. Priori, Carlo Napolitano, Nantes Referral Center for inherited cardiac arrhythmia, Carlo de Asmundis, Pedro Brugada, Ramon Brugada, Elena Arbelo, Josep Brugada, Philippe Mabo, Nathalie Behar, Carla Giustetto, Maria Sabater Molina, Juan R. Gimeno, Can Hasdemir, Peter J. Schwartz, Lia Crotti, Pascal P. McKeown, Sanjay Sharma, Elijah R. Behr, Michel Haissaguerre, Frédéric Sacher, Caroline Rooryck, Hanno L. Tan, Carol A. Remme, Pieter G. Postema, Mario Delmar, Patrick T. Ellinor, Steven A. Lubitz, Jean-Baptiste Gourraud, Michael W. Tanck, Alfred L. George Jr., Calum A. MacRae, Paul W. Burridge, Christian Dina, Vincent Probst, Arthur A. Wilde, Jean-Jacques Schott, Richard Redon &, and Connie R. Bezzina
Abstract: Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.
Published: 2022

20. Critical appraisal of technologies to assess electrical activity during atrial fibrillation:a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology

Author: de Groot, Natasja M.S., Shah, Dipen, Boyle, Patrick M., Anter, Elad, Clifford, Gari D., Deisenhofer, Isabel, Deneke, Thomas, van Dessel, Pascal, Doessel, Olaf, Dilaveris, Polychronis, Heinzel, Frank R., Kapa, Suraj, Lambiase, Pier D., Lumens, Joost, Platonov, Pyotr G., Ngarmukos, Tachapong, Martinez, Juan Pablo, Sanchez, Alejandro Olaya, Takahashi, Yoshihide, Valdigem, Bruno P., van der Veen, Alle Jan, Vernooy, Kevin, Casado-Arroyo, Ruben, De Potter, Tom, Dinov, Borislav, Kosiuk, Jedrzej, Linz, Dominik, Neubeck, Lis, Svennberg, Emma, Kim, Young Hoon, Wan, Elaine, Lopez-Cabanillas, Nestor, Locati, Emanuela T., Macfarlane, Peter, de Groot, Natasja M.S., Shah, Dipen, Boyle, Patrick M., Anter, Elad, Clifford, Gari D., Deisenhofer, Isabel, Deneke, Thomas, van Dessel, Pascal, Doessel, Olaf, Dilaveris, Polychronis, Heinzel, Frank R., Kapa, Suraj, Lambiase, Pier D., Lumens, Joost, Platonov, Pyotr G., Ngarmukos, Tachapong, Martinez, Juan Pablo, Sanchez, Alejandro Olaya, Takahashi, Yoshihide, Valdigem, Bruno P., van der Veen, Alle Jan, Vernooy, Kevin, Casado-Arroyo, Ruben, De Potter, Tom, Dinov, Borislav, Kosiuk, Jedrzej, Linz, Dominik, Neubeck, Lis, Svennberg, Emma, Kim, Young Hoon, Wan, Elaine, Lopez-Cabanillas, Nestor, Locati, Emanuela T., and Macfarlane, Peter
Abstract: We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near f
Published: 2022

21. Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

Author: Arts-assistenten Kinderen, Gezonde Vaten, Circulatory Health, Team Medisch, Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramirez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, Munroe, Patricia B, Arts-assistenten Kinderen, Gezonde Vaten, Circulatory Health, Team Medisch, Young, William J, Lahrouchi, Najim, Isaacs, Aaron, Duong, ThuyVy, Foco, Luisa, Ahmed, Farah, Brody, Jennifer A, Salman, Reem, Noordam, Raymond, Benjamins, Jan-Walter, Haessler, Jeffrey, Lyytikäinen, Leo-Pekka, Repetto, Linda, Concas, Maria Pina, van den Berg, Marten E, Weiss, Stefan, Baldassari, Antoine R, Bartz, Traci M, Cook, James P, Evans, Daniel S, Freudling, Rebecca, Hines, Oliver, Isaksen, Jonas L, Lin, Honghuang, Mei, Hao, Moscati, Arden, Müller-Nurasyid, Martina, Nursyifa, Casia, Qian, Yong, Richmond, Anne, Roselli, Carolina, Ryan, Kathleen A, Tarazona-Santos, Eduardo, Thériault, Sébastien, van Duijvenboden, Stefan, Warren, Helen R, Yao, Jie, Raza, Dania, Aeschbacher, Stefanie, Ahlberg, Gustav, Alonso, Alvaro, Andreasen, Laura, Bis, Joshua C, Boerwinkle, Eric, Campbell, Archie, Catamo, Eulalia, Cocca, Massimiliano, Cutler, Michael J, Darbar, Dawood, De Grandi, Alessandro, De Luca, Antonio, Ding, Jun, Ellervik, Christina, Ellinor, Patrick T, Felix, Stephan B, Froguel, Philippe, Fuchsberger, Christian, Gögele, Martin, Graff, Claus, Graff, Mariaelisa, Guo, Xiuqing, Hansen, Torben, Heckbert, Susan R, Huang, Paul L, Huikuri, Heikki V, Hutri-Kähönen, Nina, Ikram, M Arfan, Jackson, Rebecca D, Junttila, Juhani, Kavousi, Maryam, Kors, Jan A, Leal, Thiago P, Lemaitre, Rozenn N, Lin, Henry J, Lind, Lars, Linneberg, Allan, Liu, Simin, MacFarlane, Peter W, Mangino, Massimo, Meitinger, Thomas, Mezzavilla, Massimo, Mishra, Pashupati P, Mitchell, Rebecca N, Mononen, Nina, Montasser, May E, Morrison, Alanna C, Nauck, Matthias, Nauffal, Victor, Navarro, Pau, Nikus, Kjell, Pare, Guillaume, Patton, Kristen K, Pelliccione, Giulia, Pittman, Alan, Porteous, David J, Pramstaller, Peter P, Preuss, Michael H, Raitakari, Olli T, Reiner, Alexander P, Ribeiro, Antonio Luiz P, Rice, Kenneth M, Risch, Lorenz, Schlessinger, David, Schotten, Ulrich, Schurmann, Claudia, Shen, Xia, Shoemaker, M Benjamin, Sinagra, Gianfranco, Sinner, Moritz F, Soliman, Elsayed Z, Stoll, Monika, Strauch, Konstantin, Tarasov, Kirill, Taylor, Kent D, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Weng, Lu-Chen, Whitsel, Eric A, Wilson, James G, Avery, Christy L, Conen, David, Correa, Adolfo, Cucca, Francesco, Dörr, Marcus, Gharib, Sina A, Girotto, Giorgia, Grarup, Niels, Hayward, Caroline, Jamshidi, Yalda, Järvelin, Marjo-Riitta, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lima-Costa, Maria Fernanda, Liu, Yongmei, Loos, Ruth J F, Lubitz, Steven A, Mook-Kanamori, Dennis O, Morris, Andrew P, O'Connell, Jeffrey R, Olesen, Morten Salling, Orini, Michele, Padmanabhan, Sandosh, Pattaro, Cristian, Peters, Annette, Psaty, Bruce M, Rotter, Jerome I, Stricker, Bruno, van der Harst, Pim, van Duijn, Cornelia M, Verweij, Niek, Wilson, James F, Arking, Dan E, Ramirez, Julia, Lambiase, Pier D, Sotoodehnia, Nona, Mifsud, Borbala, Newton-Cheh, Christopher, and Munroe, Patricia B
Published: 2022

22. 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.
Abstract: Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
Published: 2021
Full Text: View/download PDF

23. 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.
Abstract: Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
Published: 2021
Full Text: View/download PDF

24. 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.
Abstract: Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
Published: 2021
Full Text: View/download PDF

25. The year in cardiovascular medicine 2020: arrhythmias

Author: Crijns, Harry J. G. M., Crijns, Harry J. G. M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, Brugada, Josep, Crijns, Harry J. G. M., Crijns, Harry J. G. M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, and Brugada, Josep
Published: 2021

26. The year in cardiovascular medicine 2020: arrhythmias

Author: Crijns, Harry J. G. M., Crijns, Harry J. G. M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, Brugada, Josep, Crijns, Harry J. G. M., Crijns, Harry J. G. M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, and Brugada, Josep
Published: 2021

27. The year in cardiovascular medicine 2020: arrhythmias

Author: Crijns, Harry J. G. M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, Brugada, Josep, Crijns, Harry J. G. M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, and Brugada, Josep
Abstract: Summary of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3 , 4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25 , 26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE-DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58
Published: 2021

28. 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.
Abstract: Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
Published: 2021
Full Text: View/download PDF

29. 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, Bezzina, Connie R., 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, Skoric-Milosavljevic, Doris, Krijger, Christian, Arbelo, Elena, Babuty, Dominique, Barajas-Martinez, Hector, Beckmann, Britt M., Bezieau, Stephane, 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., Ortuno, Cristina Gil, Giustetto, Carla, Gourraud, Jean-Baptiste, Hazeki, Daisuke, Horie, Minoru, Ishikawa, Taisuke, Itoh, Hideki, Kaneko, Yoshiaki, Kanters, Jorgen 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, Raphael P., Mazzanti, Andrea, Mörner, Stellan, Napolitano, Carlo, Ohkubo, Kimie, Papadakis, Michael, Rudic, Boris, Molina, Maria Sabater, Sacher, Frederic, 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., Kaeaeb, 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, Behr, Elijah R., Barc, Julien, and Bezzina, Connie R.
Abstract: Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
Published: 2021
Full Text: View/download PDF

30. No Clinically Relevant Effect of Heart Rate Increase and Heart Rate Recovery During Exercise on Cardiovascular Disease: A Mendelian Randomization Analysis

Author: Onderzoek Vrouw Hart & Vaatziekten, Onderzoek Precision medicine, Mensah-Kane, Josephine, Schmidt, Amand F., Hingorani, Aroon D., Finan, Chris, Chen, Yutang, van Duijvenboden, Stefan, Orini, Michele, Lambiase, Pier D., Tinker, Andrew, Marouli, Eirini, Munroe, Patricia B., Ramírez, Julia, Onderzoek Vrouw Hart & Vaatziekten, Onderzoek Precision medicine, Mensah-Kane, Josephine, Schmidt, Amand F., Hingorani, Aroon D., Finan, Chris, Chen, Yutang, van Duijvenboden, Stefan, Orini, Michele, Lambiase, Pier D., Tinker, Andrew, Marouli, Eirini, Munroe, Patricia B., and Ramírez, Julia
Published: 2021

31. The year in cardiovascular medicine 2020: arrhythmias

Author: Crijns, Harry J.G.M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, Brugada, Josep, Crijns, Harry J.G.M., Prinzen, Frits, Lambiase, Pier D., Sanders, Prashanthan, and Brugada, Josep
Abstract: Summary of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3,4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25,26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE--DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58 (Graphical Abstract–see in original.)
Published: 2021

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

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

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

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

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

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

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

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

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

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
Full Text: View/download PDF

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

Author: Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Published: 2020

38. Continued misuse of orphan drug legislation:a life-threatening risk for mexiletine

Author: Postema, Pieter G, Schwartz, Peter J, Arbelo, Elena, Bannenberg, Wilbert J, Behr, Elijah R, Belhassen, Bernard, Brugada, Josep, Brugada, Pedro, John Camm, A, Casado-Arroyo, Ruben, 't Hoen, Ellen, Hollak, Carla E M, Kääb, Stefan, Lambiase, Pier D, Leenhardt, Antoine, Priori, Silvia G, Probst, Vincent, Stunnenberg, Bas C, Tfelt-Hansen, Jacob, Van Engelen, Baziel G M, Veltmann, Christian, Viskin, Sami, Wilde, Arthur A M, Postema, Pieter G, Schwartz, Peter J, Arbelo, Elena, Bannenberg, Wilbert J, Behr, Elijah R, Belhassen, Bernard, Brugada, Josep, Brugada, Pedro, John Camm, A, Casado-Arroyo, Ruben, 't Hoen, Ellen, Hollak, Carla E M, Kääb, Stefan, Lambiase, Pier D, Leenhardt, Antoine, Priori, Silvia G, Probst, Vincent, Stunnenberg, Bas C, Tfelt-Hansen, Jacob, Van Engelen, Baziel G M, Veltmann, Christian, Viskin, Sami, and Wilde, Arthur A M
Published: 2020

39. Continued misuse of orphan drug legislation:a life-threatening risk for mexiletine

Author: Postema, Pieter G, Schwartz, Peter J, Arbelo, Elena, Bannenberg, Wilbert J, Behr, Elijah R, Belhassen, Bernard, Brugada, Josep, Brugada, Pedro, John Camm, A, Casado-Arroyo, Ruben, 't Hoen, Ellen, Hollak, Carla E M, Kääb, Stefan, Lambiase, Pier D, Leenhardt, Antoine, Priori, Silvia G, Probst, Vincent, Stunnenberg, Bas C, Tfelt-Hansen, Jacob, Van Engelen, Baziel G M, Veltmann, Christian, Viskin, Sami, Wilde, Arthur A M, Postema, Pieter G, Schwartz, Peter J, Arbelo, Elena, Bannenberg, Wilbert J, Behr, Elijah R, Belhassen, Bernard, Brugada, Josep, Brugada, Pedro, John Camm, A, Casado-Arroyo, Ruben, 't Hoen, Ellen, Hollak, Carla E M, Kääb, Stefan, Lambiase, Pier D, Leenhardt, Antoine, Priori, Silvia G, Probst, Vincent, Stunnenberg, Bas C, Tfelt-Hansen, Jacob, Van Engelen, Baziel G M, Veltmann, Christian, Viskin, Sami, and Wilde, Arthur A M
Published: 2020

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

Author: Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco, Fabiola M., Foco, Luisa, Gogele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kahonen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O'Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Theriault, Sebastien, Hutri-Kahonen, Nina, Lehtimaki, Terho, Lyytikainen, Leo-Pekka, Raitakari, Olli T., Barnes, Catriona L. K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert, V, Bottinger, Erwin P., Loos, Ruth J. F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Mueller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kaab, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Shoemaker, M. Benjamin, Smith, J. Gustav, Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Jukema, J. Wouter, Macfarlane, Peter W., Trompet, Stella, Doerr, Marcus, Felix, Stephan B., Voelker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Saaksjarvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome, I, Taylor, Kent D., Yao, Jie, de Mutsert, Renee, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill, V, Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, Andre, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Said, M. Abdullah, van der Ende, M. Yldau, Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
Published: 2020
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41. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author: Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., Munroe, Patricia B., Ntalla, Ioanna, Weng, Lu Chen, Cartwright, James H., Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R., Choi, Seung Hoan, Chaffin, Mark D., Roselli, Carolina, Barnes, Michael R., Mifsud, Borbala, Warren, Helen R., Hayward, Caroline, Marten, Jonathan, Cranley, James J., Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M., Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P., Souza, Renan P., Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P., Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A., Cook, James P., Lind, Lars, Lindgren, Cecilia M., Sundström, Johan, Nelson, Christopher P., Riaz, Muhammad B., Samani, Nilesh J., Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P., Mononen, Nina, Nikus, Kjell, Caulfield, Mark J., Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E., O’Connell, Jeff R., Ryan, Kathleen, Shuldiner, Alan R., Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo Pekka, Raitakari, Olli T., Barnes, Catriona L.K., Campbell, Harry, Joshi, Peter K., Wilson, James F., Isaacs, Aaron, Kors, Jan A., van Duijn, Cornelia M., Huang, Paul L., Gudnason, Vilmundur, Harris, Tamara B., Launer, Lenore J., Smith, Albert V., Bottinger, Erwin P., Loos, Ruth J.F., Nadkarni, Girish N., Preuss, Michael H., Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D., Rienstra, Michiel, van de Vegte, Yordi J., van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F., Strauch, Konstantin, Cutler, Michael J., Fatkin, Diane, London, Barry, Olesen, Morten, Roden, Dan M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, Mary L., Bis, Joshua C., Brody, Jennifer A., Psaty, Bruce M., Rice, Kenneth, Sotoodehnia, Nona, De Grandi, Alessandro, Fuchsberger, Christian, Pattaro, Cristian, Pramstaller, Peter P., Ford, Ian, Wouter Jukema, J., Macfarlane, Peter W., Trompet, Stella, Dörr, Marcus, Felix, Stephan B., Völker, Uwe, Weiss, Stefan, Havulinna, Aki S., Jula, Antti, Sääksjärvi, Katri, Salomaa, Veikko, Guo, Xiuqing, Heckbert, Susan R., Lin, Henry J., Rotter, Jerome I., Taylor, Kent D., Yao, Jie, de Mutsert, Renée, Maan, Arie C., Mook-Kanamori, Dennis O., Noordam, Raymond, Cucca, Francesco, Ding, Jun, Lakatta, Edward G., Qian, Yong, Tarasov, Kirill V., Levy, Daniel, Lin, Honghuang, Newton-Cheh, Christopher H., Lunetta, Kathryn L., Murray, Alison D., Porteous, David J., Smith, Blair H., Stricker, Bruno H., Uitterlinden, André, van den Berg, Marten E., Haessler, Jeffrey, Jackson, Rebecca D., Kooperberg, Charles, Peters, Ulrike, Reiner, Alexander P., Whitsel, Eric A., Alonso, Alvaro, Arking, Dan E., Boerwinkle, Eric, Ehret, Georg B., Soliman, Elsayed Z., Avery, Christy L., Gogarten, Stephanie M., Kerr, Kathleen F., Laurie, Cathy C., Seyerle, Amanda A., Stilp, Adrienne, Assa, Solmaz, Abdullah Said, M., Yldau van der Ende, M., Lambiase, Pier D., Orini, Michele, Ramirez, Julia, Van Duijvenboden, Stefan, Arnar, David O., Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Thorleifsson, Gudmar, Thorolfsdottir, Rosa B., Thorsteinsdottir, Unnur, Benjamin, Emelia J., Tinker, Andrew, Stefansson, Kari, Ellinor, Patrick T., Jamshidi, Yalda, Lubitz, Steven A., and Munroe, Patricia B.
Abstract: The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Published: 2020

42. Impact of body mass index on the outcomes of catheter ablation of atrial fibrillation: A European observational multicenter study

Author: Providência, Rui, Adragão, Pedro, Asmundis, Carlo de, Chun, Kyoung-Ryul Julian, Chierchia, Gianbattista, Defaye, Pascal, Anselme, Frederic, Creta, Antonio, Lambiase, Pier D., Schmidt, Boris, Chen, Shaojie, Cavaco, Diogo, Hunter, Ross J., Carmo, João, Combes, Stephane, Honarbakhsh, Shohreh, Combes, Nicolas, Sousa, Maria João, Jebberi, Zeynab, Albenque, Jean-Paul, Boveda, Serge, Providência, Rui, Adragão, Pedro, Asmundis, Carlo de, Chun, Kyoung-Ryul Julian, Chierchia, Gianbattista, Defaye, Pascal, Anselme, Frederic, Creta, Antonio, Lambiase, Pier D., Schmidt, Boris, Chen, Shaojie, Cavaco, Diogo, Hunter, Ross J., Carmo, João, Combes, Stephane, Honarbakhsh, Shohreh, Combes, Nicolas, Sousa, Maria João, Jebberi, Zeynab, Albenque, Jean-Paul, and Boveda, Serge
Abstract: Background: Outcomes of catheter ablation of atrial fibrillation (AF) are variable and the predictors of success require further elucidation since the identification of correctable risk factors could help to optimize therapy. We aimed to assess the impact of body mass index (BMI) in the overall safety and efficacy of catheter ablation of AF, with emphasis on the use of cryoballoon ablation and novel oral anticoagulants. Methods and Results: There were 2497 consecutive patients undergoing catheter ablation of AF in 7 European high volume centers were stratified according to BMI (normal weight <25 kg/m2, pre‐obese 25–30 kg/m2, obesity 30–35 kg/m2, and morbid obesity ≥35 kg/m2) and comparisons of procedural outcomes evaluated. Pre‐obese and obese patients presented more comorbidities (hypertension, diabetes mellitus, and sleep apnea), and had higher rates of non‐paroxysmal AF ablation procedures. The rate of atrial 12‐month arrhythmia relapse increased alongside with BMI (35.2%, 35.7%, 43.6%, and 48.0% P<0.001). During a median follow‐up of 18.8 months (interquartile range 11–28), after adjusting for all baseline differences, BMI was an independent predictor of relapse (hazard ratio=1.01 per kg/m2; 95% CI 1.01–1.02; P=0.002), adding incremental predictive value to obstructive sleep apnea. BMI was not a predictor for any of the reported complications. Using novel oral anticoagulants and cryoballoon ablation was safe and efficacy was comparable with vitamin‐K antagonists and radiofrequency ablation. Conclusions: Obese patients present with a more adverse comorbidity profile, more advanced forms of AF, and have lower chances of being free from AF relapse after ablation. Use of novel oral anticoagulants and cryoballoon ablation may be an option in this patient group.
Published: 2019

43. Definition and treatment of arrhythmogenic cardiomyopathy: an updated expert panel report

Author: Elliott, Perry M, Anastasakis, Aris, Asimaki, Angeliki, Basso, Cristina, Bauce, Barbara, Brooke, Matthew A, Calkins, Hugh, Corrado, Domenico, Duru, Firat, Green, Kathleen J, Judge, Daniel P, Kelsell, David, Lambiase, Pier D, McKenna, William J, Pilichou, Kalliopi, Protonotarios, Alexandros, Saffitz, Jeffrey E, Syrris, Petros, Tandri, Hari, Te Riele, Anneline, Thiene, Gaetano, Tsatsopoulou, Adalena, van Tintelen, J Peter, Elliott, Perry M, Anastasakis, Aris, Asimaki, Angeliki, Basso, Cristina, Bauce, Barbara, Brooke, Matthew A, Calkins, Hugh, Corrado, Domenico, Duru, Firat, Green, Kathleen J, Judge, Daniel P, Kelsell, David, Lambiase, Pier D, McKenna, William J, Pilichou, Kalliopi, Protonotarios, Alexandros, Saffitz, Jeffrey E, Syrris, Petros, Tandri, Hari, Te Riele, Anneline, Thiene, Gaetano, Tsatsopoulou, Adalena, and van Tintelen, J Peter
Abstract: It is 35 years since the first description of arrhythmogenic right ventricular cardiomyopathy (ARVC) and more than 20 years since the first reports establishing desmosomal gene mutations as a major cause of the disease. Early advances in the understanding of the clinical, pathological and genetic architecture of ARVC resulted in consensus diagnostic criteria, which proved to be sensitive but not entirely specific for the disease. In more recent years, clinical and genetic data from families and the recognition of a much broader spectrum of structural disorders affecting both ventricles and associated with a propensity to ventricular arrhythmia have raised many questions about pathogenesis, disease terminology and clinical management. In this paper, we present the conclusions of an expert round table that aimed to summarise the current state of the art in arrhythmogenic cardiomyopathies and to define future research priorities.
Published: 2019

44. Definition and treatment of arrhythmogenic cardiomyopathy: an updated expert panel report

Author: UMC Utrecht, Team Onderzoek, Genetica, Elliott, Perry M., Anastasakis, Aris, Asimaki, Angeliki, Basso, Cristina, Bauce, Barbara, Brooke, Matthew A., Calkins, Hugh, Corrado, Domenico, Duru, Firat, Green, Kathleen J., Judge, Daniel P., Kelsell, David, Lambiase, Pier D., McKenna, William J., Pilichou, Kalliopi, Protonotarios, Alexandros, Saffitz, Jeffrey E., Syrris, Petros, Tandri, Hari, Te Riele, Anneline, Thiene, Gaetano, Tsatsopoulou, Adalena, van Tintelen, J. Peter, UMC Utrecht, Team Onderzoek, Genetica, Elliott, Perry M., Anastasakis, Aris, Asimaki, Angeliki, Basso, Cristina, Bauce, Barbara, Brooke, Matthew A., Calkins, Hugh, Corrado, Domenico, Duru, Firat, Green, Kathleen J., Judge, Daniel P., Kelsell, David, Lambiase, Pier D., McKenna, William J., Pilichou, Kalliopi, Protonotarios, Alexandros, Saffitz, Jeffrey E., Syrris, Petros, Tandri, Hari, Te Riele, Anneline, Thiene, Gaetano, Tsatsopoulou, Adalena, and van Tintelen, J. Peter
Published: 2019

45. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., Jamshidi, Yalda, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., and Jamshidi, Yalda
Published: 2018

46. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., Jamshidi, Yalda, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., and Jamshidi, Yalda
Published: 2018

47. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., Jamshidi, Yalda, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., and Jamshidi, Yalda
Published: 2018

48. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6.

Author: Prins, Bram P, Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J, Prins, Bram P, Prins, Bram P, Mead, Timothy J, Brody, Jennifer A, Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A, van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T, Gabriel, George C, Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M, Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching-Ti, Lyytikäinen, Leo-Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V, Verweij, Niek, Warren, Helen R, Weiss, Stefan, Alonso, Alvaro, Arnar, David O, Bots, Michiel L, de Boer, Rudolf A, Dominiczak, Anna F, Eijgelsheim, Mark, Ellinor, Patrick T, Guo, Xiuqing, Felix, Stephan B, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Huang, Paul L, Jukema, JW, Kähönen, Mika, Kors, Jan A, Lambiase, Pier D, Launer, Lenore J, Li, Man, Linneberg, Allan, Nelson, Christopher P, Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M, Raitakari, Olli T, Rice, Kenneth M, Rotter, Jerome I, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Tim D, Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G, Xie, Zhijun, Asselbergs, Folkert W, Dörr, Marcus, van Duijn, Cornelia M, Gasparini, Paolo, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K, Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J, Lubitz, Steven A, Mook-Kanamori, Dennis O, Conti, Francesco J, Newton-Cheh, Christopher H, Rosand, Jonathan, Rudan, Igor, and Samani, Nilesh J
Abstract: BackgroundGenome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.ResultsHere, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.ConclusionsOur approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
Published: 2018

49. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Onderzoek Precision medicine, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., Jamshidi, Yalda, Onderzoek Precision medicine, Cardiovasculaire Epi Team 5, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Team Medisch, Prins, Bram P., Mead, Timothy J., Brody, Jennifer A., Sveinbjornsson, Gardar, Ntalla, Ioanna, Bihlmeyer, Nathan A., van den Berg, Marten, Bork-Jensen, Jette, Cappellani, Stefania, Van Duijvenboden, Stefan, Klena, Nikolai T., Gabriel, George C., Liu, Xiaoqin, Gulec, Cagri, Grarup, Niels, Haessler, Jeffrey, Hall, Leanne M., Iorio, Annamaria, Isaacs, Aaron, Li-Gao, Ruifang, Lin, Honghuang, Liu, Ching Ti, Lyytikäinen, Leo Pekka, Marten, Jonathan, Mei, Hao, Müller-Nurasyid, Martina, Orini, Michele, Padmanabhan, Sandosh, Radmanesh, Farid, Ramirez, Julia, Robino, Antonietta, Schwartz, Molly, van Setten, Jessica, Smith, Albert V., Verweij, Niek, Warren, Helen R., Weiss, Stefan, Alonso, Alvaro, Arnar, David O., Bots, Michiel L., de Boer, Rudolf A., Dominiczak, Anna F., Eijgelsheim, Mark, Ellinor, Patrick T., Guo, Xiuqing, Felix, Stephan B., Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Huang, Paul L., Jukema, J. W., Kähönen, Mika, Kors, Jan A., Lambiase, Pier D., Launer, Lenore J., Li, Man, Linneberg, Allan, Nelson, Christopher P., Pedersen, Oluf, Perez, Marco, Peters, Annette, Polasek, Ozren, Psaty, Bruce M., Raitakari, Olli T., Rice, Kenneth M., Rotter, Jerome I., Sinner, Moritz F., Soliman, Elsayed Z., Spector, Tim D., Strauch, Konstantin, Thorsteinsdottir, Unnur, Tinker, Andrew, Trompet, Stella, Uitterlinden, André, Vaartjes, Ilonca, van der Meer, Peter, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Wilson, James G., Xie, Zhijun, Asselbergs, Folkert W., Dörr, Marcus, van Duijn, Cornelia M., Gasparini, Paolo, Gudbjartsson, Daniel F., Gudnason, Vilmundur, Hansen, Torben, Kääb, Stefan, Kanters, Jørgen K., Kooperberg, Charles, Lehtimäki, Terho, Lin, Henry J., Lubitz, Steven A., Mook-Kanamori, Dennis O., Conti, Francesco J., Newton-Cheh, Christopher H., Rosand, Jonathan, Rudan, Igor, Samani, Nilesh J., Sinagra, Gianfranco, Smith, Blair H., Holm, Hilma, Stricker, Bruno H., Ulivi, Sheila, Sotoodehnia, Nona, Apte, Suneel S., van der Harst, Pim, Stefansson, Kari, Munroe, Patricia B., Arking, Dan E., Lo, Cecilia W., and Jamshidi, Yalda
Published: 2018

50. Complex regional pain syndrome: Facilitating the use of self-management strategies

Author: Dao, XCJ., Blais-Hébert, R., Duranleau, L., Marie-Pier, D., Litowski, J., Turbide, J., Bussières, A., Dao, XCJ., Blais-Hébert, R., Duranleau, L., Marie-Pier, D., Litowski, J., Turbide, J., and Bussières, A.
Published: 2017

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