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Pregled bibliografske jedinice broj: 1253213

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

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. et al.
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction // Nature communications, 11 (2020), 1; 2542, 12 doi:10.1038/s41467-020-15706-x (međunarodna recenzija, članak, znanstveni)

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

Autori
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 ; Kolčić, Ivana ; Polašek, 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.

Izvornik
Nature communications (2041-1723) 11 (2020), 1; 2542, 12

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
GENOME-WIDE ASSOCIATION ; ATRIAL-FIBRILLATION ; MUTATIONS ; RISK ; DURATION ; CARDIOMYOPATHY ; CALCINEURIN ; BRADYCARDIA ; DECREASE ; ELEMENTS

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA

Ustanove:
Medicinski fakultet, Split

Profili:

Avatar Url Ivana Kolčić (autor)

Avatar Url Ozren Polašek (autor)

Poveznice na cjeloviti tekst rada:

doi www.nature.com

Citiraj ovu publikaciju:

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. et al.
Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction // Nature communications, 11 (2020), 1; 2542, 12 doi:10.1038/s41467-020-15706-x (međunarodna recenzija, članak, znanstveni)
Ntalla, I., Weng, L., Cartwright, J., Hall, A., Sveinbjornsson, G., Tucker, N., Choi, S., Chaffin, M., Roselli, C. & Barnes, M. (2020) Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction. Nature communications, 11 (1), 2542, 12 doi:10.1038/s41467-020-15706-x.
@article{article, author = {Ntalla, Ioanna and Weng, Lu-Chen and Cartwright, James H. and Hall, Amelia Weber and Sveinbjornsson, Gardar and Tucker, Nathan R. and Choi, Seung Hoan and Chaffin, Mark D. and Roselli, Carolina and Barnes, Michael R. and Mifsud, Borbala and Warren, Helen R. and Hayward, Caroline and Marten, Jonathan and Cranley, James J. and Concas, Maria Pina and Gasparini, Paolo and Boutin, Thibaud and Kol\v{c}i\'{c}, Ivana and Pola\v{s}ek, Ozren and Rudan, Igor and Araujo, Nathalia M. and Lima-Costa, Maria Fernanda and Ribeiro, Antonio Luiz P. and Souza, Renan P. and Tarazona-Santos, Eduardo and Giedraitis, Vilmantas and Ingelsson, Erik and Mahajan, Anubha and Morris, Andrew P. and Del Greco M, Fabiola and Foco, Luisa and G\"{o}gele, Martin and Hicks, Andrew A. and Cook, James P. and Lind, Lars and Lindgren, Cecilia M. and Sundstr\"{o}m, Johan and Nelson, Christopher P. and Riaz, Muhammad B. and Samani, Nilesh J. and Sinagra, Gianfranco and Ulivi, Sheila and K\"{a}h\"{o}nen, Mika and Mishra, Pashupati P. and Mononen, Nina and Nikus, Kjell and Caulfield, Mark J. and Dominiczak, Anna and Padmanabhan, Sandosh and Montasser, May E. and O’Connell, Jeff R. and Ryan, Kathleen and Shuldiner, Alan R. and Aeschbacher, Stefanie and Conen, David and Risch, Lorenz and Th\'{e}riault, S\'{e}bastien and Hutri-K\"{a}h\"{o}nen, Nina and Lehtim\"{a}ki, Terho and Lyytik\"{a}inen, Leo-Pekka and Raitakari, Olli T. and Barnes, Catriona L. K. and Campbell, Harry and Joshi, Peter K. and Wilson, James F. and Isaacs, Aaron and Kors, Jan A. and van Duijn, Cornelia M. and Huang, Paul L. and Gudnason, Vilmundur and Harris, Tamara B. and Launer, Lenore J. and Smith, Albert V. and Bottinger, Erwin P. and Loos, Ruth J. F. and Nadkarni, Girish N. and Preuss, Michael H. and Correa, Adolfo and Mei, Hao and Wilson, James and Meitinger, Thomas and M\"{u}ller-Nurasyid, Martina and Peters, Annette and Waldenberger, Melanie and Mangino, Massimo and Spector, Timothy D. and Rienstra, Michiel and van de Vegte, Yordi J. and van der Harst, Pim and Verweij, Niek and K\"{a}\"{a}b, Stefan and Schramm, Katharina and Sinner, Moritz F. and Strauch, Konstantin and Cutler, Michael J. and Fatkin, Diane and London, Barry and Olesen, Morten and Roden, Dan M. and Benjamin Shoemaker, M. and Gustav Smith, J. and Biggs, Mary L. and Bis, Joshua C. and Brody, Jennifer A. and Psaty, Bruce M. and Rice, Kenneth and Sotoodehnia, Nona and De Grandi, Alessandro and Fuchsberger, Christian and Pattaro, Cristian and Pramstaller, Peter P. and Ford, Ian and Wouter Jukema, J. and Macfarlane, Peter W. and Trompet, Stella and D\"{o}rr, Marcus and Felix, Stephan B. and V\"{o}lker, Uwe and Weiss, Stefan and Havulinna, Aki S. and Jula, Antti and S\"{a}\"{a}ksj\"{a}rvi, Katri and Salomaa, Veikko and Guo, Xiuqing and Heckbert, Susan R. and Lin, Henry J. and Rotter, Jerome I. and Taylor, Kent D. and Yao, Jie and de Mutsert, Ren\'{e}e and Maan, Arie C. and Mook- Kanamori, Dennis O. and Noordam, Raymond and Cucca, Francesco and Ding, Jun and Lakatta, Edward G. and Qian, Yong and Tarasov, Kirill V. and Levy, Daniel and Lin, Honghuang and Newton-Cheh, Christopher H. and Lunetta, Kathryn L. and Murray, Alison D. and Porteous, David J. and Smith, Blair H. and Stricker, Bruno H. and Uitterlinden, Andr\'{e} and van den Berg, Marten E. and Haessler, Jeffrey and Jackson, Rebecca D. and Kooperberg, Charles and Peters, Ulrike and Reiner, Alexander P. and Whitsel, Eric A. and Alonso, Alvaro and Arking, Dan E. and Boerwinkle, Eric and Ehret, Georg B. and Soliman, Elsayed Z. and Avery, Christy L. and Gogarten, Stephanie M. and Kerr, Kathleen F. and Laurie, Cathy C. and Seyerle, Amanda A. and Stilp, Adrienne and Assa, Solmaz and Abdullah Said, M. and Yldau van der Ende, M. and Lambiase, Pier D. and Orini, Michele and Ramirez, Julia and Van Duijvenboden, Stefan and Arnar, David O. and Gudbjartsson, Daniel F. and Holm, Hilma and Sulem, Patrick and Thorleifsson, Gudmar and Thorolfsdottir, Rosa B. and Thorsteinsdottir, Unnur and Benjamin, Emelia J. and Tinker, Andrew and Stefansson, Kari and Ellinor, Patrick T. and Jamshidi, Yalda and Lubitz, Steven A. and Munroe, Patricia B.}, year = {2020}, pages = {12}, DOI = {10.1038/s41467-020-15706-x}, chapter = {2542}, keywords = {GENOME-WIDE ASSOCIATION, ATRIAL-FIBRILLATION, MUTATIONS, RISK, DURATION, CARDIOMYOPATHY, CALCINEURIN, BRADYCARDIA, DECREASE, ELEMENTS}, journal = {Nature communications}, doi = {10.1038/s41467-020-15706-x}, volume = {11}, number = {1}, issn = {2041-1723}, title = {Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction}, keyword = {GENOME-WIDE ASSOCIATION, ATRIAL-FIBRILLATION, MUTATIONS, RISK, DURATION, CARDIOMYOPATHY, CALCINEURIN, BRADYCARDIA, DECREASE, ELEMENTS}, chapternumber = {2542} }
@article{article, author = {Ntalla, Ioanna and Weng, Lu-Chen and Cartwright, James H. and Hall, Amelia Weber and Sveinbjornsson, Gardar and Tucker, Nathan R. and Choi, Seung Hoan and Chaffin, Mark D. and Roselli, Carolina and Barnes, Michael R. and Mifsud, Borbala and Warren, Helen R. and Hayward, Caroline and Marten, Jonathan and Cranley, James J. and Concas, Maria Pina and Gasparini, Paolo and Boutin, Thibaud and Kol\v{c}i\'{c}, Ivana and Pola\v{s}ek, Ozren and Rudan, Igor and Araujo, Nathalia M. and Lima-Costa, Maria Fernanda and Ribeiro, Antonio Luiz P. and Souza, Renan P. and Tarazona-Santos, Eduardo and Giedraitis, Vilmantas and Ingelsson, Erik and Mahajan, Anubha and Morris, Andrew P. and Del Greco M, Fabiola and Foco, Luisa and G\"{o}gele, Martin and Hicks, Andrew A. and Cook, James P. and Lind, Lars and Lindgren, Cecilia M. and Sundstr\"{o}m, Johan and Nelson, Christopher P. and Riaz, Muhammad B. and Samani, Nilesh J. and Sinagra, Gianfranco and Ulivi, Sheila and K\"{a}h\"{o}nen, Mika and Mishra, Pashupati P. and Mononen, Nina and Nikus, Kjell and Caulfield, Mark J. and Dominiczak, Anna and Padmanabhan, Sandosh and Montasser, May E. and O’Connell, Jeff R. and Ryan, Kathleen and Shuldiner, Alan R. and Aeschbacher, Stefanie and Conen, David and Risch, Lorenz and Th\'{e}riault, S\'{e}bastien and Hutri-K\"{a}h\"{o}nen, Nina and Lehtim\"{a}ki, Terho and Lyytik\"{a}inen, Leo-Pekka and Raitakari, Olli T. and Barnes, Catriona L. K. and Campbell, Harry and Joshi, Peter K. and Wilson, James F. and Isaacs, Aaron and Kors, Jan A. and van Duijn, Cornelia M. and Huang, Paul L. and Gudnason, Vilmundur and Harris, Tamara B. and Launer, Lenore J. and Smith, Albert V. and Bottinger, Erwin P. and Loos, Ruth J. F. and Nadkarni, Girish N. and Preuss, Michael H. and Correa, Adolfo and Mei, Hao and Wilson, James and Meitinger, Thomas and M\"{u}ller-Nurasyid, Martina and Peters, Annette and Waldenberger, Melanie and Mangino, Massimo and Spector, Timothy D. and Rienstra, Michiel and van de Vegte, Yordi J. and van der Harst, Pim and Verweij, Niek and K\"{a}\"{a}b, Stefan and Schramm, Katharina and Sinner, Moritz F. and Strauch, Konstantin and Cutler, Michael J. and Fatkin, Diane and London, Barry and Olesen, Morten and Roden, Dan M. and Benjamin Shoemaker, M. and Gustav Smith, J. and Biggs, Mary L. and Bis, Joshua C. and Brody, Jennifer A. and Psaty, Bruce M. and Rice, Kenneth and Sotoodehnia, Nona and De Grandi, Alessandro and Fuchsberger, Christian and Pattaro, Cristian and Pramstaller, Peter P. and Ford, Ian and Wouter Jukema, J. and Macfarlane, Peter W. and Trompet, Stella and D\"{o}rr, Marcus and Felix, Stephan B. and V\"{o}lker, Uwe and Weiss, Stefan and Havulinna, Aki S. and Jula, Antti and S\"{a}\"{a}ksj\"{a}rvi, Katri and Salomaa, Veikko and Guo, Xiuqing and Heckbert, Susan R. and Lin, Henry J. and Rotter, Jerome I. and Taylor, Kent D. and Yao, Jie and de Mutsert, Ren\'{e}e and Maan, Arie C. and Mook- Kanamori, Dennis O. and Noordam, Raymond and Cucca, Francesco and Ding, Jun and Lakatta, Edward G. and Qian, Yong and Tarasov, Kirill V. and Levy, Daniel and Lin, Honghuang and Newton-Cheh, Christopher H. and Lunetta, Kathryn L. and Murray, Alison D. and Porteous, David J. and Smith, Blair H. and Stricker, Bruno H. and Uitterlinden, Andr\'{e} and van den Berg, Marten E. and Haessler, Jeffrey and Jackson, Rebecca D. and Kooperberg, Charles and Peters, Ulrike and Reiner, Alexander P. and Whitsel, Eric A. and Alonso, Alvaro and Arking, Dan E. and Boerwinkle, Eric and Ehret, Georg B. and Soliman, Elsayed Z. and Avery, Christy L. and Gogarten, Stephanie M. and Kerr, Kathleen F. and Laurie, Cathy C. and Seyerle, Amanda A. and Stilp, Adrienne and Assa, Solmaz and Abdullah Said, M. and Yldau van der Ende, M. and Lambiase, Pier D. and Orini, Michele and Ramirez, Julia and Van Duijvenboden, Stefan and Arnar, David O. and Gudbjartsson, Daniel F. and Holm, Hilma and Sulem, Patrick and Thorleifsson, Gudmar and Thorolfsdottir, Rosa B. and Thorsteinsdottir, Unnur and Benjamin, Emelia J. and Tinker, Andrew and Stefansson, Kari and Ellinor, Patrick T. and Jamshidi, Yalda and Lubitz, Steven A. and Munroe, Patricia B.}, year = {2020}, pages = {12}, DOI = {10.1038/s41467-020-15706-x}, chapter = {2542}, keywords = {GENOME-WIDE ASSOCIATION, ATRIAL-FIBRILLATION, MUTATIONS, RISK, DURATION, CARDIOMYOPATHY, CALCINEURIN, BRADYCARDIA, DECREASE, ELEMENTS}, journal = {Nature communications}, doi = {10.1038/s41467-020-15706-x}, volume = {11}, number = {1}, issn = {2041-1723}, title = {Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction}, keyword = {GENOME-WIDE ASSOCIATION, ATRIAL-FIBRILLATION, MUTATIONS, RISK, DURATION, CARDIOMYOPATHY, CALCINEURIN, BRADYCARDIA, DECREASE, ELEMENTS}, chapternumber = {2542} }

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