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

Autor: Dennis O. Mook-Kanamori, Yalda Jamshidi, Peter K. Joshi, Seung Hoan Choi, Henry J. Lin, Rebecca D. Jackson, Alison D. Murray, May E. Montasser, Veikko Salomaa, Charles Kooperberg, Moritz F. Sinner, Gianfranco Sinagra, Luisa Foco, James G. Wilson, Johan Sundström, Kathleen A. Ryan, Eric A. Whitsel, Bruno H. Stricker, Sandosh Padmanabhan, Christopher Newton-Cheh, Ozren Polasek, Unnur Thorsteinsdottir, Niek Verweij, Pier D. Lambiase, Nathan R. Tucker, Stefan Kääb, Jun Ding, Stefan Weiss, Daniel F. Gudbjartsson, David Conen, Lars Lind, Ivana Kolcic, Lu-Chen Weng, J. Wouter Jukema, Kirill V. Tarasov, Xiuqing Guo, Stella Trompet, Patricia B. Munroe, Albert V. Smith, Elsayed Z. Soliman, Andrew Tinker, Antti Jula, J. Gustav Smith, Alexander P. Reiner, Sébastien Thériault, Kathryn L. Lunetta, Vilmundur Gudnason, Mika Kähönen, Massimo Mangino, Raymond Noordam, Joshua C. Bis, Alan R. Shuldiner, Tim D. Spector, Borbala Mifsud, Stefan van Duijvenboden, Jeffrey R. O'Connell, Emelia J. Benjamin, M. Benjamin Shoemaker, Stephan B. Felix, Peter W. Macfarlane, Lorenz Risch, Uwe Völker, Stephanie M. Gogarten, Maria Fernanda Lima-Costa, Julia Ramirez, Morten S. Olesen, Konstantin Strauch, Annette Peters, Aaron Isaacs, Steven A. Lubitz, Eric Boerwinkle, Carolina Roselli, James H. Cartwright, Nathalia M. Araujo, Ruth J. F. Loos, Diane Fatkin, Harry Campbell, Blair H. Smith, Thomas Meitinger, André G. Uitterlinden, Paul L. Huang, Tamara B. Harris, Kathleen F. Kerr, David J. Porteous, Martina Müller-Nurasyid, Francesco Cucca, Michiel Rienstra, Davíð O. Arnar, Amanda A. Seyerle, Caroline Hayward, M. Abdullah Said, Catriona L. K. Barnes, Kent D. Taylor, Nona Sotoodehnia, Nina Mononen, Dan M. Roden, Jonathan Marten, Terho Lehtimäki, Dan E. Arking, Anna F. Dominiczak, Jan A. Kors, Olli T. Raitakari, Igor Rudan, Yordi J. van de Vegte, Christopher P. Nelson, Erik Ingelsson, Ulrike Peters, Girish N. Nadkarni, Eduardo Tarazona-Santos, Edward G. Lakatta, Nina Hutri-Kähönen, Bruce M. Psaty, Patrick T. Ellinor, Christian Fuchsberger, Katharina Schramm, Amelia W. Hall, M. Yldau van der Ende, Alvaro Alonso, James F. Wilson, Sheila Ulivi, Rosa B. Thorolfsdottir, Stefanie Aeschbacher, Mary L. Biggs, Marten E. van den Berg, Nilesh J. Samani, Thibaud Boutin, Vilmantas Giedraitis, Honghuang Lin, Kjell Nikus, Helen R. Warren, Arie C. Maan, James J. Cranley, Adolfo Correa, Martin Gögele, Ian Ford, Katri Sääksjärvi, Georg Ehret, Michele Orini, Susan R. Heckbert, Cecilia M. Lindgren, Jie Yao, Maria Pina Concas, Pim van der Harst, Ioanna Ntalla, Jeffrey Haessler, Jerome I. Rotter, Pashupati P. Mishra, Michael J. Cutler, Erwin P. Bottinger, Cornelia M. van Duijn, Jennifer A. Brody, Paolo Gasparini, Lenore J. Launer, Andrew P. Morris, Renée de Mutsert, Aki S. Havulinna, James P. Cook, Hilma Holm, Patrick Sulem, Alessandro De Grandi, Cristian Pattaro, Gardar Sveinbjornsson, Antonio Luiz Pinho Ribeiro, Mark J. Caulfield, Gudmar Thorleifsson, Marcus Dörr, Muhammad B. Riaz, Peter P. Pramstaller, Yong Qian, Anubha Mahajan, Cathy C. Laurie, Kenneth Rice, Mark Chaffin, Kari Stefansson, Andrew A. Hicks, Solmaz Assa, Hao Mei, Leo-Pekka Lyytikäinen, Fabiola Del Greco M, Renan P. Souza, Michael Preuss, Adrienne M. Stilp, Barry London, Melanie Waldenberger, Christy L. Avery, Daniel Levy, Michael R. Barnes
Přispěvatelé: Medical Informatics, Epidemiology, Internal Medicine, Weng, Lu-Chen [0000-0003-1475-4930], Hall, Amelia Weber [0000-0002-7915-0313], Tucker, Nathan R [0000-0002-5071-4218], Chaffin, Mark D [0000-0002-1234-5562], Roselli, Carolina [0000-0001-5267-6756], Barnes, Michael R [0000-0001-9097-7381], Mifsud, Borbala [0000-0003-3429-3094], Hayward, Caroline [0000-0002-9405-9550], Concas, Maria Pina [0000-0003-3598-2537], Boutin, Thibaud [0000-0003-4754-1675], Kolcic, Ivana [0000-0001-7918-6052], Rudan, Igor [0000-0001-6993-6884], Souza, Renan P [0000-0002-9479-4432], Giedraitis, Vilmantas [0000-0003-3423-2021], Ingelsson, Erik [0000-0003-2256-6972], Mahajan, Anubha [0000-0001-5585-3420], Morris, Andrew P [0000-0002-6805-6014], Hicks, Andrew A [0000-0001-6320-0411], Sundström, Johan [0000-0003-2247-8454], Nelson, Christopher P [0000-0001-8025-2897], Riaz, Muhammad B [0000-0002-5512-1745], Sinagra, Gianfranco [0000-0003-2700-8478], Mishra, Pashupati P [0000-0001-5177-3431], Caulfield, Mark J [0000-0001-9295-3594], Dominiczak, Anna [0000-0003-4913-3608], Risch, Lorenz [0000-0003-2692-6699], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Isaacs, Aaron [0000-0001-5037-4834], van Duijn, Cornelia M [0000-0002-2374-9204], Gudnason, Vilmundur [0000-0001-5696-0084], Smith, Albert V [0000-0003-1942-5845], Loos, Ruth JF [0000-0002-8532-5087], Preuss, Michael H [0000-0001-5266-8465], Correa, Adolfo [0000-0002-9501-600X], Müller-Nurasyid, Martina [0000-0003-3793-5910], Waldenberger, Melanie [0000-0003-0583-5093], Mangino, Massimo [0000-0002-2167-7470], Rienstra, Michiel [0000-0002-2581-070X], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Fatkin, Diane [0000-0002-9010-9856], Brody, Jennifer A [0000-0001-8509-148X], Rice, Kenneth [0000-0002-3071-7278], Pattaro, Cristian [0000-0002-4119-0109], Wouter Jukema, J [0000-0002-3246-8359], Weiss, Stefan [0000-0002-3553-4315], Havulinna, Aki S [0000-0002-4787-8959], Sääksjärvi, Katri [0000-0002-5061-4911], Salomaa, Veikko [0000-0001-7563-5324], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Lakatta, Edward G [0000-0002-4772-0035], Lin, Honghuang [0000-0003-3043-3942], Lunetta, Kathryn L [0000-0002-9268-810X], Murray, Alison D [0000-0003-4915-4847], Porteous, David J [0000-0003-1249-6106], Smith, Blair H [0000-0002-5362-9430], Uitterlinden, André [0000-0002-7276-3387], Peters, Ulrike [0000-0001-5666-9318], Alonso, Alvaro [0000-0002-2225-8323], Ehret, Georg B [0000-0002-5730-0675], Soliman, Elsayed Z [0000-0001-5632-8150], Gogarten, Stephanie M [0000-0002-7231-9745], Kerr, Kathleen F [0000-0002-6438-9583], Abdullah Said, M [0000-0003-2920-7745], Orini, Michele [0000-0001-5773-0344], Ramirez, Julia [0000-0003-4130-5866], Van Duijvenboden, Stefan [0000-0001-8897-558X], Gudbjartsson, Daniel F [0000-0002-5222-9857], Sulem, Patrick [0000-0001-7123-6123], Thorolfsdottir, Rosa B [0000-0001-7475-0398], Benjamin, Emelia J [0000-0003-4076-2336], Stefansson, Kari [0000-0003-1676-864X], Ellinor, Patrick T [0000-0002-2067-0533], Jamshidi, Yalda [0000-0003-0151-6482], Lubitz, Steven A [0000-0002-9599-4866], Munroe, Patricia B [0000-0002-4176-2947], Apollo - University of Cambridge Repository, Medicum, Institute for Molecular Medicine Finland, Complex Disease Genetics, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Cardiovascular Centre (CVC), Ntalla, I., Weng, L. -C., Cartwright, J. H., Hall, A. W., Sveinbjornsson, G., Tucker, N. R., Choi, S. H., Chaffin, M. D., Roselli, C., Barnes, M. R., Mifsud, B., Warren, H. R., Hayward, C., Marten, J., Cranley, J. J., Concas, M. P., Gasparini, P., Boutin, T., Kolcic, I., Polasek, O., Rudan, I., Araujo, N. M., Lima-Costa, M. F., Ribeiro, A. L. P., Souza, R. P., Tarazona-Santos, E., Giedraitis, V., Ingelsson, E., Mahajan, A., Morris, A. P., Del Greco M, F., Foco, L., Gogele, M., Hicks, A. A., Cook, J. P., Lind, L., Lindgren, C. M., Sundstrom, J., Nelson, C. P., Riaz, M. B., Samani, N. J., Sinagra, G., Ulivi, S., Kahonen, M., Mishra, P. P., Mononen, N., Nikus, K., Caulfield, M. J., Dominiczak, A., Padmanabhan, S., Montasser, M. E., O'Connell, J. R., Ryan, K., Shuldiner, A. R., Aeschbacher, S., Conen, D., Risch, L., Theriault, S., Hutri-Kahonen, N., Lehtimaki, T., Lyytikainen, L. -P., Raitakari, O. T., Barnes, C. L. K., Campbell, H., Joshi, P. K., Wilson, J. F., Isaacs, A., Kors, J. A., van Duijn, C. M., Huang, P. L., Gudnason, V., Harris, T. B., Launer, L. J., Smith, A. V., Bottinger, E. P., Loos, R. J. F., Nadkarni, G. N., Preuss, M. H., Correa, A., Mei, H., Wilson, J., Meitinger, T., Muller-Nurasyid, M., Peters, A., Waldenberger, M., Mangino, M., Spector, T. D., Rienstra, M., van de Vegte, Y. J., van der Harst, P., Verweij, N., Kaab, S., Schramm, K., Sinner, M. F., Strauch, K., Cutler, M. J., Fatkin, D., London, B., Olesen, M., Roden, D. M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, M. L., Bis, J. C., Brody, J. A., Psaty, B. M., Rice, K., Sotoodehnia, N., De Grandi, A., Fuchsberger, C., Pattaro, C., Pramstaller, P. P., Ford, I., Wouter Jukema, J., Macfarlane, P. W., Trompet, S., Dorr, M., Felix, S. B., Volker, U., Weiss, S., Havulinna, A. S., Jula, A., Saaksjarvi, K., Salomaa, V., Guo, X., Heckbert, S. R., Lin, H. J., Rotter, J. I., Taylor, K. D., Yao, J., de Mutsert, R., Maan, A. C., Mook-Kanamori, D. O., Noordam, R., Cucca, F., Ding, J., Lakatta, E. G., Qian, Y., Tarasov, K. V., Levy, D., Lin, H., Newton-Cheh, C. H., Lunetta, K. L., Murray, A. D., Porteous, D. J., Smith, B. H., Stricker, B. H., Uitterlinden, A., van den Berg, M. E., Haessler, J., Jackson, R. D., Kooperberg, C., Peters, U., Reiner, A. P., Whitsel, E. A., Alonso, A., Arking, D. E., Boerwinkle, E., Ehret, G. B., Soliman, E. Z., Avery, C. L., Gogarten, S. M., Kerr, K. F., Laurie, C. C., Seyerle, A. A., Stilp, A., Assa, S., Abdullah Said, M., Yldau van der Ende, M., Lambiase, P. D., Orini, M., Ramirez, J., Van Duijvenboden, S., Arnar, D. O., Gudbjartsson, D. F., Holm, H., Sulem, P., Thorleifsson, G., Thorolfsdottir, R. B., Thorsteinsdottir, U., Benjamin, E. J., Tinker, A., Stefansson, K., Ellinor, P. T., Jamshidi, Y., Lubitz, S. A., Munroe, P. B., Fysiologie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Háskóli Íslands, University of Iceland
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Multifactorial Inheritance
General Physics and Astronomy
Gene Expression
Genome-wide association study
030204 cardiovascular system & hematology
Arrhythmias
Genome-wide association studies
CALCINEURIN
Electrocardiography
0302 clinical medicine
Cardiovascular Disease
Multi-ancestry GWAS
ELEMENTS
Medicine
Cardiac and Cardiovascular Systems
Blóðrásarsjúkdómar
lcsh:Science
RISK
DECREASE
education.field_of_study
Multidisciplinary
Kardiologi
medicine.diagnostic_test
1184 Genetics
developmental biology
physiology
Atrial fibrillation
3142 Public health care science
environmental and occupational health
3. Good health
Endophenotype
Arrhythmias
Cardiac
Cardiovascular Diseases
Endophenotypes
Female
Genetic Loci
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Quantitative Trait Loci
cardiovascular system
Cardiology
medicine.symptom
Erfðarannsóknir
Cardiac
Medical Genetics
Human
Bradycardia
medicine.medical_specialty
Science
GENOME-WIDE ASSOCIATION
ATRIAL-FIBRILLATION
MUTATIONS
DURATION
CARDIOMYOPATHY
BRADYCARDIA
Population
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
Cardiac conduction
PR interval
education
Medicinsk genetik
business.industry
Cardiovascular genetics
General Chemistry
Arfgengi
medicine.disease
030104 developmental biology
lcsh:Q
business
Zdroj: Nature Communications, 11(1). Nature Publishing Group
Nature Communications, 11(1):2542. Nature Publishing Group
Nature Communications
Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020)
Nature Communications, 11(1). NATURE PUBLISHING GROUP
Ntalla, I, Weng, L-C, Cartwright, J H, Hall, A W, Sveinbjornsson, G, Tucker, N R, Choi, S H, Chaffin, M D, Roselli, C, Barnes, M R, Mifsud, B, Warren, H R, Hayward, C, Marten, J, Cranley, J J, Concas, M P, Gasparini, P, Boutin, T, Kolcic, I, Rudan, I, Araujo, N M, Lima-Costa, M F, Ribeiro, A L P, Souza, R P, Tarazona-Santos, E, Giedraitis, V, Ingelsson, E, Mahajan, A, Morris, A P, Del Greco M, F, Foco, L, Gögele, M, Hicks, A A, Lind, L, Lindgren, C M, Sundström, J, Nelson, C P, Riaz, M B, Samani, N J, Sinagra, G, Ulivi, S, Kähönen, M, Mishra, P P, Mononen, N, Nikus, K, Caulfield, M J, Dominiczak, A, Padmanabhan, S, Montasser, M E, O'Connell, J R, Ryan, K, Shuldiner, A R, Aeschbacher, S, Conen, D, Risch, L, Thériault, S, Hutri-Kähönen, N, Lehtimäki, T, Lyytikäinen, L-P, Raitakari, O T, Barnes, C L K, Campbell, H, Joshi, P K, Wilson, J, Isaacs, A, Kors, J A, van Duijn, C M, Huang, P L, Gudnason, V, Harris, T B, Launer, L J, Smith, A V, Bottinger, E P, Loos, R J F, Nadkarni, G N, Preuss, M H, Correa, A, Mei, H, Wilson, J, Meitinger, T, Müller-Nurasyid, M, Peters, A, Waldenberger, M, Mangino, M, Spector, T D, Rienstra, M, van de Vegte, Y J, van der Harst, P, Verweij, N, Kääb, S, Schramm, K, Sinner, M F, Strauch, K, Cutler, M J, Fatkin, D, London, B, Olesen, M, Roden, D M, Benjamin Shoemaker, M, Gustav Smith, J, Biggs, M L, Bis, J C, Brody, J A, Psaty, B M, Rice, K, Sotoodehnia, N, De Grandi, A, Fuchsberger, C, Pattaro, C, Pramstaller, P P, Ford, I, Wouter Jukema, J, Macfarlane, P W, Trompet, S, Dörr, M, Felix, S B, Völker, U, Weiss, S, Havulinna, A S, Jula, A, Sääksjärvi, K, Salomaa, V, Guo, X, Heckbert, S R, Lin, H J, Rotter, J I, Taylor, K D, Yao, J, de Mutsert, R, Maan, A C, Mook-Kanamori, D O, Noordam, R, Cucca, F, Ding, J, Lakatta, E G, Qian, Y, Tarasov, K V, Levy, D, Lin, H, Newton-Cheh, C H, Lunetta, K L, Murray, A D, Porteous, D J, Smith, B H, Stricker, B H, Uitterlinden, A, van den Berg, M E, Haessler, J, Jackson, R D, Kooperberg, C, Peters, U, Reiner, A P, Whitsel, E A, Alonso, A, Arking, D E, Boerwinkle, E, Ehret, G B, Soliman, E Z, Avery, C L, Gogarten, S M, Kerr, K F, Laurie, C C, Seyerle, A A, Stilp, A, Assa, S, Abdullah Said, M, Yldau van der Ende, M, Lambiase, P D, Orini, M, Ramirez, J, Van Duijvenboden, S, Arnar, D O, Gudbjartsson, D F, Holm, H, Sulem, P, Thorleifsson, G, Thorolfsdottir, R B, Thorsteinsdottir, U, Benjamin, E J, Tinker, A, Stefansson, K, Ellinor, P T, Jamshidi, Y, Lubitz, S A & Munroe, P B 2020, ' Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction ', Nature Communications, vol. 11, no. 1, pp. 2542 . https://doi.org/10.1038/s41467-020-15706-x
Ntalla, I, Weng, L C, Cartwright, J H, Hall, A W, Sveinbjornsson, G, Tucker, N R, Choi, S H, Chaffin, M D, Roselli, C, Barnes, M R, Mifsud, B, Warren, H R, Hayward, C, Marten, J, Cranley, J J, Concas, M P, Gasparini, P, Boutin, T, Kolcic, I, Polasek, O, Rudan, I, Araujo, N M, Lima-Costa, M F, Ribeiro, A L P, Souza, R P, Tarazona-Santos, E, Giedraitis, V, Ingelsson, E, Mahajan, A, Morris, A P, Del Greco M, F, Foco, L, Gögele, M, Hicks, A A, Cook, J P, Lind, L, Lindgren, C M, Sundström, J, Nelson, C P, Riaz, M B, Samani, N J, Sinagra, G, Ulivi, S, Kähönen, M, Mishra, P P, Mononen, N, Nikus, K, Caulfield, M J, Dominiczak, A, Padmanabhan, S, Montasser, M E, O’Connell, J R, Ryan, K, Shuldiner, A R, Aeschbacher, S, Conen, D, Risch, L, Thériault, S, Hutri-Kähönen, N, Lehtimäki, T, Lyytikäinen, L P, Raitakari, O T, Barnes, C L K, Campbell, H, Joshi, P K, Wilson, J F, Isaacs, A, Kors, J A, van Duijn, C M, Huang, P L, Gudnason, V, Harris, T B, Launer, L J, Smith, A V, Bottinger, E P, Loos, R J F, Nadkarni, G N, Preuss, M H, Correa, A, Mei, H, Wilson, J, Meitinger, T, Müller-Nurasyid, M, Peters, A, Waldenberger, M, Mangino, M, Spector, T D, Rienstra, M, van de Vegte, Y J, van der Harst, P, Verweij, N, Kääb, S, Schramm, K, Sinner, M F, Strauch, K, Cutler, M J, Fatkin, D, London, B, Olesen, M, Roden, D M, Benjamin Shoemaker, M, Gustav Smith, J, Biggs, M L, Bis, J C, Brody, J A, Psaty, B M, Rice, K, Sotoodehnia, N, De Grandi, A, Fuchsberger, C, Pattaro, C, Pramstaller, P P, Ford, I, Wouter Jukema, J, Macfarlane, P W, Trompet, S, Dörr, M, Felix, S B, Völker, U, Weiss, S, Havulinna, A S, Jula, A, Sääksjärvi, K, Salomaa, V, Guo, X, Heckbert, S R, Lin, H J, Rotter, J I, Taylor, K D, Yao, J, de Mutsert, R, Maan, A C, Mook-Kanamori, D O, Noordam, R, Cucca, F, Ding, J, Lakatta, E G, Qian, Y, Tarasov, K V, Levy, D, Lin, H, Newton-Cheh, C H, Lunetta, K L, Murray, A D, Porteous, D J, Smith, B H, Stricker, B H, Uitterlinden, A, van den Berg, M E, Haessler, J, Jackson, R D, Kooperberg, C, Peters, U, Reiner, A P, Whitsel, E A, Alonso, A, Arking, D E, Boerwinkle, E, Ehret, G B, Soliman, E Z, Avery, C L, Gogarten, S M, Kerr, K F, Laurie, C C, Seyerle, A A, Stilp, A, Assa, S, Abdullah Said, M, Yldau van der Ende, M, Lambiase, P D, Orini, M, Ramirez, J, Van Duijvenboden, S, Arnar, D O, Gudbjartsson, D F, Holm, H, Sulem, P, Thorleifsson, G, Thorolfsdottir, R B, Thorsteinsdottir, U, Benjamin, E J, Tinker, A, Stefansson, K, Ellinor, P T, Jamshidi, Y, Lubitz, S A & Munroe, P B 2020, ' Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction ', Nature Communications, vol. 11, no. 1, 2542 . https://doi.org/10.1038/s41467-020-15706-x
Ntalla, I, Weng, L-C, Cartwright, J H, Hall, A W, Sveinbjornsson, G, Tucker, N R, Choi, S H, Chaffin, M D, Roselli, C, Barnes, M R, Mifsud, B, Warren, H R, Hayward, C, Marten, J, Cranley, J J, Concas, M P, Gasparini, P, Boutin, T, Kolcic, I, Polasek, O, Rudan, I, Araujo, N M, Lima-Costa, M F, Ribeiro, A L P, Souza, R P, Tarazona-Santos, E, Giedraitis, V, Ingelsson, E, Mahajan, A, Morris, A P, Del Greco M, F, Foco, L, Gögele, M, Hicks, A A, Cook, J P, Lind, L, Lindgren, C M, Sundström, J, Nelson, C P, Riaz, M B, Samani, N J, Sinagra, G, Ulivi, S, Kähönen, M, Mishra, P P, Mononen, N, Nikus, K, Caulfield, M J, Dominiczak, A, Padmanabhan, S, Montasser, M E, O'Connell, J R, Ryan, K, Shuldiner, A R, Aeschbacher, S, Conen, D, Risch, L, Thériault, S, Hutri-Kähönen, N, Lehtimäki, T, Lyytikäinen, L-P, Raitakari, O T, Barnes, C L K, Campbell, H, Joshi, P K, Wilson, J F, Isaacs, A, Kors, J A, van Duijn, C M, Huang, P L, Gudnason, V, Harris, T B, Launer, L J, Smith, A V, Bottinger, E P, Loos, R J F, Nadkarni, G N, Preuss, M H, Correa, A, Mei, H, Wilson, J, Meitinger, T, Müller-Nurasyid, M, Peters, A, Waldenberger, M, Mangino, M, Spector, T D, Rienstra, M, van de Vegte, Y J, van der Harst, P, Verweij, N, Kääb, S, Schramm, K, Sinner, M F, Strauch, K, Cutler, M J, Fatkin, D, London, B, Olesen, M, Roden, D M, Benjamin Shoemaker, M, Gustav Smith, J, Biggs, M L, Bis, J C, Brody, J A, Psaty, B M, Rice, K, Sotoodehnia, N, De Grandi, A, Fuchsberger, C, Pattaro, C, Pramstaller, P P, Ford, I, Wouter Jukema, J, Macfarlane, P W, Trompet, S, Dörr, M, Felix, S B, Völker, U, Weiss, S, Havulinna, A S, Jula, A, Sääksjärvi, K, Salomaa, V, Guo, X, Heckbert, S R, Lin, H J, Rotter, J I, Taylor, K D, Yao, J, de Mutsert, R, Maan, A C, Mook-Kanamori, D O, Noordam, R, Cucca, F, Ding, J, Lakatta, E G, Qian, Y, Tarasov, K V, Levy, D, Lin, H, Newton-Cheh, C H, Lunetta, K L, Murray, A D, Porteous, D J, Smith, B H, Stricker, B H, Uitterlinden, A, van den Berg, M E, Haessler, J, Jackson, R D, Kooperberg, C, Peters, U, Reiner, A P, Whitsel, E A, Alonso, A, Arking, D E, Boerwinkle, E, Ehret, G B, Soliman, E Z, Avery, C L, Gogarten, S M, Kerr, K F, Laurie, C C, Seyerle, A A, Stilp, A, Assa, S, Abdullah Said, M, Yldau van der Ende, M, Lambiase, P D, Orini, M, Ramirez, J, Van Duijvenboden, S, Arnar, D O, Gudbjartsson, D F, Holm, H, Sulem, P, Thorleifsson, G, Thorolfsdottir, R B, Thorsteinsdottir, U, Benjamin, E J, Tinker, A, Stefansson, K, Ellinor, P T, Jamshidi, Y, Lubitz, S A & Munroe, P B 2020, ' Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction ', Nature Communications, vol. 11, no. 1, pp. 2542 . https://doi.org/10.1038/s41467-020-15706-x
ISSN: 2041-1723
Popis: Publisher's version (útgefin grein)
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.
We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.
Databáze: OpenAIRE
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