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

Ingrid E. Christophersen; Michiel Rienstra; Carolina Roselli; Xiaoyan Yin; Bastiaan Geelhoed; John Barnard; Honghuang Lin; Dan E. Arking; Albert V. Smith; Christine M. Albert; Mark Chaffin; Nathan R. Tucker; Molong Li; Derek Klarin; Nathan A. Bihlmeyer; Siew Kee Low; Peter E. Weeke; Martina Müller-Nurasyid; J. Gustav Smith; Jennifer A. Brody; Maartje N. Niemeijer; Marcus Dörr; Stella Trompet; Jennifer Huffman; Stefan Gustafsson; Claudia Schurmann; Marcus E. Kleber; Leo Pekka Lyytikäinen; Ilkka Seppälä; Rainer Malik; Andrea R.V.R. Horimoto; Marco Perez; Juha Sinisalo; Stefanie Aeschbacher; Sébastien Thériault; Jie Yao; Farid Radmanesh; Stefan Weiss; Alexander Teumer; Seung Hoan Choi; Lu Chen Weng; Sebastian Clauss; Rajat Deo; Daniel J. Rader; Svati H. Shah; Albert Sun; Jemma C. Hopewell; Stephanie Debette; Ganesh Chauhan; Qiong Yang; Bradford B. Worrall; Guillaume Paré; Yoichiro Kamatani; Yanick P. Hagemeijer; Niek Verweij; Joylene E. Siland; Michiaki Kubo; Jonathan D. Smith; David R. Van Wagoner; Joshua C. Bis; Siegfried Perz; Bruce M. Psaty; Paul M. Ridker; Jared W. Magnani; Tamara B. Harris; Lenore J. Launer; M. Benjamin Shoemaker; Sandosh Padmanabhan; Jeffrey Haessler; Traci M. Bartz; Melanie Waldenberger; Peter Lichtner; Marina Arendt; Jose E. Krieger; Mika Kähönen; Lorenz Risch; Alfredo J. Mansur; Annette Peters; Blair H. Smith; Lars Lind; Stuart A. Scott; Yingchang Lu; Erwin B. Bottinger; Jussi Hernesniemi; Cecilia M. Lindgren; Jorge A. Wong; Jie Huang; Markku Eskola; Andrew P. Morris; Ian Ford; Alex P. Reiner; Graciela Delgado; Lin Y. Chen; Yii Der Ida Chen; Roopinder K. Sandhu; Man Li; Eric Boerwinkle; Lewin Eisele; Lars Lannfelt; Natalia Rost; Christopher D. Anderson; Kent D. Taylor; Archie Campbell; Patrik K. Magnusson; David Porteous; Lynne J. Hocking; Efthymia Vlachopoulou; Nancy L. Pedersen; Kjell Nikus; Marju Orho-Melander; Anders Hamsten; Jan Heeringa; Joshua C. Denny; Jennifer Kriebel; Dawood Darbar; Christopher Newton-Cheh; Christian Shaffer; Peter W. Macfarlane; Stefanie Heilmann-Heimbach; Peter Almgren; Paul L. Huang; Nona Sotoodehnia; Elsayed Z. Soliman; Andre G. Uitterlinden; Albert Hofman; Oscar H. Franco; Uwe Völker; Karl Heinz Jöckel; Moritz F. Sinner; Henry J. Lin; Xiuqing Guo; Martin Dichgans; Erik Ingelsson; Charles Kooperberg; Olle Melander; Ruth J.F. Loos; Jari Laurikka; David Conen; Jonathan Rosand; Pim Van Der Harst; Marja Liisa Lokki; Sekar Kathiresan; Alexandre Pereira; J. Wouter Jukema; Caroline Hayward; Jerome I. Rotter; Winfried März; Terho Lehtimäki; Bruno H. Stricker; Mina K. Chung; Stephan B. Felix; Vilmundur Gudnason; Alvaro Alonso; Dan M. Roden; Stefan Kääb; Daniel I. Chasman; Susan R. Heckbert; Emelia J. Benjamin; Toshihiro Tanaka; Kathryn L. Lunetta; Steven A. Lubitz; Patrick T. Ellinor

doi:10.1038/ng.3843

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

Ingrid E. Christophersen, Michiel Rienstra, Carolina Roselli, Xiaoyan Yin, Bastiaan Geelhoed, John Barnard, Honghuang Lin, Dan E. Arking, Albert V. Smith, Christine M. Albert, Mark Chaffin, Nathan R. Tucker, Molong Li, Derek Klarin, Nathan A. Bihlmeyer, Siew Kee Low, Peter E. Weeke, Martina Müller-Nurasyid, J. Gustav Smith, Jennifer A. BrodyMaartje N. Niemeijer, Marcus Dörr, Stella Trompet, Jennifer Huffman, Stefan Gustafsson, Claudia Schurmann, Marcus E. Kleber, Leo Pekka Lyytikäinen, Ilkka Seppälä, Rainer Malik, Andrea R.V.R. Horimoto, Marco Perez, Juha Sinisalo, Stefanie Aeschbacher, Sébastien Thériault, Jie Yao, Farid Radmanesh, Stefan Weiss, Alexander Teumer, Seung Hoan Choi, Lu Chen Weng, Sebastian Clauss, Rajat Deo, Daniel J. Rader, Svati H. Shah, Albert Sun, Jemma C. Hopewell, Stephanie Debette, Ganesh Chauhan, Qiong Yang, Bradford B. Worrall, Guillaume Paré, Yoichiro Kamatani, Yanick P. Hagemeijer, Niek Verweij, Joylene E. Siland, Michiaki Kubo, Jonathan D. Smith, David R. Van Wagoner, Joshua C. Bis, Siegfried Perz, Bruce M. Psaty, Paul M. Ridker, Jared W. Magnani, Tamara B. Harris, Lenore J. Launer, M. Benjamin Shoemaker, Sandosh Padmanabhan, Jeffrey Haessler, Traci M. Bartz, Melanie Waldenberger, Peter Lichtner, Marina Arendt, Jose E. Krieger, Mika Kähönen, Lorenz Risch, Alfredo J. Mansur, Annette Peters, Blair H. Smith, Lars Lind, Stuart A. Scott, Yingchang Lu, Erwin B. Bottinger, Jussi Hernesniemi, Cecilia M. Lindgren, Jorge A. Wong, Jie Huang, Markku Eskola, Andrew P. Morris, Ian Ford, Alex P. Reiner, Graciela Delgado, Lin Y. Chen, Yii Der Ida Chen, Roopinder K. Sandhu, Man Li, Eric Boerwinkle, Lewin Eisele, Lars Lannfelt, Natalia Rost, Christopher D. Anderson, Kent D. Taylor, Archie Campbell, Patrik K. Magnusson, David Porteous, Lynne J. Hocking, Efthymia Vlachopoulou, Nancy L. Pedersen, Kjell Nikus, Marju Orho-Melander, Anders Hamsten, Jan Heeringa, Joshua C. Denny, Jennifer Kriebel, Dawood Darbar, Christopher Newton-Cheh, Christian Shaffer, Peter W. Macfarlane, Stefanie Heilmann-Heimbach, Peter Almgren, Paul L. Huang, Nona Sotoodehnia, Elsayed Z. Soliman, Andre G. Uitterlinden, Albert Hofman, Oscar H. Franco, Uwe Völker, Karl Heinz Jöckel, Moritz F. Sinner, Henry J. Lin, Xiuqing Guo, Martin Dichgans, Erik Ingelsson, Charles Kooperberg, Olle Melander, Ruth J.F. Loos, Jari Laurikka, David Conen, Jonathan Rosand, Pim Van Der Harst, Marja Liisa Lokki, Sekar Kathiresan, Alexandre Pereira, J. Wouter Jukema, Caroline Hayward, Jerome I. Rotter, Winfried März, Terho Lehtimäki, Bruno H. Stricker, Mina K. Chung, Stephan B. Felix, Vilmundur Gudnason, Alvaro Alonso, Dan M. Roden, Stefan Kääb, Daniel I. Chasman, Susan R. Heckbert, Emelia J. Benjamin, Toshihiro Tanaka, Kathryn L. Lunetta, Steven A. Lubitz, Patrick T. Ellinor

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Abstract

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

Original language	English
Pages (from-to)	946-952
Number of pages	7
Journal	Nature Genetics
Volume	49
Issue number	6
DOIs	https://doi.org/10.1038/ng.3843
Publication status	Published - 01-06-2017

All Science Journal Classification (ASJC) codes

Genetics

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10.1038/ng.3843

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Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., Lin, H., Arking, D. E., Smith, A. V., Albert, C. M., Chaffin, M., Tucker, N. R., Li, M., Klarin, D., Bihlmeyer, N. A., Low, S. K., Weeke, P. E., Müller-Nurasyid, M., Smith, J. G., ... Ellinor, P. T. (2017). Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nature Genetics, 49(6), 946-952. https://doi.org/10.1038/ng.3843

Christophersen, Ingrid E. ; Rienstra, Michiel ; Roselli, Carolina ; Yin, Xiaoyan ; Geelhoed, Bastiaan ; Barnard, John ; Lin, Honghuang ; Arking, Dan E. ; Smith, Albert V. ; Albert, Christine M. ; Chaffin, Mark ; Tucker, Nathan R. ; Li, Molong ; Klarin, Derek ; Bihlmeyer, Nathan A. ; Low, Siew Kee ; Weeke, Peter E. ; Müller-Nurasyid, Martina ; Smith, J. Gustav ; Brody, Jennifer A. ; Niemeijer, Maartje N. ; Dörr, Marcus ; Trompet, Stella ; Huffman, Jennifer ; Gustafsson, Stefan ; Schurmann, Claudia ; Kleber, Marcus E. ; Lyytikäinen, Leo Pekka ; Seppälä, Ilkka ; Malik, Rainer ; Horimoto, Andrea R.V.R. ; Perez, Marco ; Sinisalo, Juha ; Aeschbacher, Stefanie ; Thériault, Sébastien ; Yao, Jie ; Radmanesh, Farid ; Weiss, Stefan ; Teumer, Alexander ; Choi, Seung Hoan ; Weng, Lu Chen ; Clauss, Sebastian ; Deo, Rajat ; Rader, Daniel J. ; Shah, Svati H. ; Sun, Albert ; Hopewell, Jemma C. ; Debette, Stephanie ; Chauhan, Ganesh ; Yang, Qiong ; Worrall, Bradford B. ; Paré, Guillaume ; Kamatani, Yoichiro ; Hagemeijer, Yanick P. ; Verweij, Niek ; Siland, Joylene E. ; Kubo, Michiaki ; Smith, Jonathan D. ; Van Wagoner, David R. ; Bis, Joshua C. ; Perz, Siegfried ; Psaty, Bruce M. ; Ridker, Paul M. ; Magnani, Jared W. ; Harris, Tamara B. ; Launer, Lenore J. ; Shoemaker, M. Benjamin ; Padmanabhan, Sandosh ; Haessler, Jeffrey ; Bartz, Traci M. ; Waldenberger, Melanie ; Lichtner, Peter ; Arendt, Marina ; Krieger, Jose E. ; Kähönen, Mika ; Risch, Lorenz ; Mansur, Alfredo J. ; Peters, Annette ; Smith, Blair H. ; Lind, Lars ; Scott, Stuart A. ; Lu, Yingchang ; Bottinger, Erwin B. ; Hernesniemi, Jussi ; Lindgren, Cecilia M. ; Wong, Jorge A. ; Huang, Jie ; Eskola, Markku ; Morris, Andrew P. ; Ford, Ian ; Reiner, Alex P. ; Delgado, Graciela ; Chen, Lin Y. ; Chen, Yii Der Ida ; Sandhu, Roopinder K. ; Li, Man ; Boerwinkle, Eric ; Eisele, Lewin ; Lannfelt, Lars ; Rost, Natalia ; Anderson, Christopher D. ; Taylor, Kent D. ; Campbell, Archie ; Magnusson, Patrik K. ; Porteous, David ; Hocking, Lynne J. ; Vlachopoulou, Efthymia ; Pedersen, Nancy L. ; Nikus, Kjell ; Orho-Melander, Marju ; Hamsten, Anders ; Heeringa, Jan ; Denny, Joshua C. ; Kriebel, Jennifer ; Darbar, Dawood ; Newton-Cheh, Christopher ; Shaffer, Christian ; Macfarlane, Peter W. ; Heilmann-Heimbach, Stefanie ; Almgren, Peter ; Huang, Paul L. ; Sotoodehnia, Nona ; Soliman, Elsayed Z. ; Uitterlinden, Andre G. ; Hofman, Albert ; Franco, Oscar H. ; Völker, Uwe ; Jöckel, Karl Heinz ; Sinner, Moritz F. ; Lin, Henry J. ; Guo, Xiuqing ; Dichgans, Martin ; Ingelsson, Erik ; Kooperberg, Charles ; Melander, Olle ; Loos, Ruth J.F. ; Laurikka, Jari ; Conen, David ; Rosand, Jonathan ; Van Der Harst, Pim ; Lokki, Marja Liisa ; Kathiresan, Sekar ; Pereira, Alexandre ; Jukema, J. Wouter ; Hayward, Caroline ; Rotter, Jerome I. ; März, Winfried ; Lehtimäki, Terho ; Stricker, Bruno H. ; Chung, Mina K. ; Felix, Stephan B. ; Gudnason, Vilmundur ; Alonso, Alvaro ; Roden, Dan M. ; Kääb, Stefan ; Chasman, Daniel I. ; Heckbert, Susan R. ; Benjamin, Emelia J. ; Tanaka, Toshihiro ; Lunetta, Kathryn L. ; Lubitz, Steven A. ; Ellinor, Patrick T. / Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. In: Nature Genetics. 2017 ; Vol. 49, No. 6. pp. 946-952.

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title = "Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation",

abstract = "Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.",

author = "Christophersen, {Ingrid E.} and Michiel Rienstra and Carolina Roselli and Xiaoyan Yin and Bastiaan Geelhoed and John Barnard and Honghuang Lin and Arking, {Dan E.} and Smith, {Albert V.} and Albert, {Christine M.} and Mark Chaffin and Tucker, {Nathan R.} and Molong Li and Derek Klarin and Bihlmeyer, {Nathan A.} and Low, {Siew Kee} and Weeke, {Peter E.} and Martina M{\"u}ller-Nurasyid and Smith, {J. Gustav} and Brody, {Jennifer A.} and Niemeijer, {Maartje N.} and Marcus D{\"o}rr and Stella Trompet and Jennifer Huffman and Stefan Gustafsson and Claudia Schurmann and Kleber, {Marcus E.} and Lyytik{\"a}inen, {Leo Pekka} and Ilkka Sepp{\"a}l{\"a} and Rainer Malik and Horimoto, {Andrea R.V.R.} and Marco Perez and Juha Sinisalo and Stefanie Aeschbacher and S{\'e}bastien Th{\'e}riault and Jie Yao and Farid Radmanesh and Stefan Weiss and Alexander Teumer and Choi, {Seung Hoan} and Weng, {Lu Chen} and Sebastian Clauss and Rajat Deo and Rader, {Daniel J.} and Shah, {Svati H.} and Albert Sun and Hopewell, {Jemma C.} and Stephanie Debette and Ganesh Chauhan and Qiong Yang and Worrall, {Bradford B.} and Guillaume Par{\'e} and Yoichiro Kamatani and Hagemeijer, {Yanick P.} and Niek Verweij and Siland, {Joylene E.} and Michiaki Kubo and Smith, {Jonathan D.} and {Van Wagoner}, {David R.} and Bis, {Joshua C.} and Siegfried Perz and Psaty, {Bruce M.} and Ridker, {Paul M.} and Magnani, {Jared W.} and Harris, {Tamara B.} and Launer, {Lenore J.} and Shoemaker, {M. Benjamin} and Sandosh Padmanabhan and Jeffrey Haessler and Bartz, {Traci M.} and Melanie Waldenberger and Peter Lichtner and Marina Arendt and Krieger, {Jose E.} and Mika K{\"a}h{\"o}nen and Lorenz Risch and Mansur, {Alfredo J.} and Annette Peters and Smith, {Blair H.} and Lars Lind and Scott, {Stuart A.} and Yingchang Lu and Bottinger, {Erwin B.} and Jussi Hernesniemi and Lindgren, {Cecilia M.} and Wong, {Jorge A.} and Jie Huang and Markku Eskola and Morris, {Andrew P.} and Ian Ford and Reiner, {Alex P.} and Graciela Delgado and Chen, {Lin Y.} and Chen, {Yii Der Ida} and Sandhu, {Roopinder K.} and Man Li and Eric Boerwinkle and Lewin Eisele and Lars Lannfelt and Natalia Rost and Anderson, {Christopher D.} and Taylor, {Kent D.} and Archie Campbell and Magnusson, {Patrik K.} and David Porteous and Hocking, {Lynne J.} and Efthymia Vlachopoulou and Pedersen, {Nancy L.} and Kjell Nikus and Marju Orho-Melander and Anders Hamsten and Jan Heeringa and Denny, {Joshua C.} and Jennifer Kriebel and Dawood Darbar and Christopher Newton-Cheh and Christian Shaffer and Macfarlane, {Peter W.} and Stefanie Heilmann-Heimbach and Peter Almgren and Huang, {Paul L.} and Nona Sotoodehnia and Soliman, {Elsayed Z.} and Uitterlinden, {Andre G.} and Albert Hofman and Franco, {Oscar H.} and Uwe V{\"o}lker and J{\"o}ckel, {Karl Heinz} and Sinner, {Moritz F.} and Lin, {Henry J.} and Xiuqing Guo and Martin Dichgans and Erik Ingelsson and Charles Kooperberg and Olle Melander and Loos, {Ruth J.F.} and Jari Laurikka and David Conen and Jonathan Rosand and {Van Der Harst}, Pim and Lokki, {Marja Liisa} and Sekar Kathiresan and Alexandre Pereira and Jukema, {J. Wouter} and Caroline Hayward and Rotter, {Jerome I.} and Winfried M{\"a}rz and Terho Lehtim{\"a}ki and Stricker, {Bruno H.} and Chung, {Mina K.} and Felix, {Stephan B.} and Vilmundur Gudnason and Alvaro Alonso and Roden, {Dan M.} and Stefan K{\"a}{\"a}b and Chasman, {Daniel I.} and Heckbert, {Susan R.} and Benjamin, {Emelia J.} and Toshihiro Tanaka and Lunetta, {Kathryn L.} and Lubitz, {Steven A.} and Ellinor, {Patrick T.}",

year = "2017",

month = jun,

day = "1",

doi = "10.1038/ng.3843",

language = "English",

volume = "49",

pages = "946--952",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "6",

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Christophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, AV, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, SK, Weeke, PE, Müller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Dörr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikäinen, LP, Seppälä, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Thériault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Choi, SH, Weng, LC, Clauss, S, Deo, R, Rader, DJ, Shah, SH, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Paré, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, Shoemaker, MB, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kähönen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, YDI, Sandhu, RK, Li, M, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Anderson, CD, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann-Heimbach, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Völker, U, Jöckel, KH, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, Rosand, J, Van Der Harst, P, Lokki, ML, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, JI, März, W, Lehtimäki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kääb, S, Chasman, DI, Heckbert, SR, Benjamin, EJ, Tanaka, T, Lunetta, KL, Lubitz, SA & Ellinor, PT 2017, 'Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation', Nature Genetics, vol. 49, no. 6, pp. 946-952. https://doi.org/10.1038/ng.3843

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. / Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A.; Low, Siew Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurmann, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R.V.R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati H.; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge A.; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann-Heimbach, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J.F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; Van Der Harst, Pim; Lokki, Marja Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

In: Nature Genetics, Vol. 49, No. 6, 01.06.2017, p. 946-952.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

AU - Christophersen, Ingrid E.

AU - Rienstra, Michiel

AU - Roselli, Carolina

AU - Yin, Xiaoyan

AU - Geelhoed, Bastiaan

AU - Barnard, John

AU - Lin, Honghuang

AU - Arking, Dan E.

AU - Smith, Albert V.

AU - Albert, Christine M.

AU - Chaffin, Mark

AU - Tucker, Nathan R.

AU - Li, Molong

AU - Klarin, Derek

AU - Bihlmeyer, Nathan A.

AU - Low, Siew Kee

AU - Weeke, Peter E.

AU - Müller-Nurasyid, Martina

AU - Smith, J. Gustav

AU - Brody, Jennifer A.

AU - Niemeijer, Maartje N.

AU - Dörr, Marcus

AU - Trompet, Stella

AU - Huffman, Jennifer

AU - Gustafsson, Stefan

AU - Schurmann, Claudia

AU - Kleber, Marcus E.

AU - Lyytikäinen, Leo Pekka

AU - Seppälä, Ilkka

AU - Malik, Rainer

AU - Horimoto, Andrea R.V.R.

AU - Perez, Marco

AU - Sinisalo, Juha

AU - Aeschbacher, Stefanie

AU - Thériault, Sébastien

AU - Yao, Jie

AU - Radmanesh, Farid

AU - Weiss, Stefan

AU - Teumer, Alexander

AU - Choi, Seung Hoan

AU - Weng, Lu Chen

AU - Clauss, Sebastian

AU - Deo, Rajat

AU - Rader, Daniel J.

AU - Shah, Svati H.

AU - Sun, Albert

AU - Hopewell, Jemma C.

AU - Debette, Stephanie

AU - Chauhan, Ganesh

AU - Yang, Qiong

AU - Worrall, Bradford B.

AU - Paré, Guillaume

AU - Kamatani, Yoichiro

AU - Hagemeijer, Yanick P.

AU - Verweij, Niek

AU - Siland, Joylene E.

AU - Kubo, Michiaki

AU - Smith, Jonathan D.

AU - Van Wagoner, David R.

AU - Bis, Joshua C.

AU - Perz, Siegfried

AU - Psaty, Bruce M.

AU - Ridker, Paul M.

AU - Magnani, Jared W.

AU - Harris, Tamara B.

AU - Launer, Lenore J.

AU - Shoemaker, M. Benjamin

AU - Padmanabhan, Sandosh

AU - Haessler, Jeffrey

AU - Bartz, Traci M.

AU - Waldenberger, Melanie

AU - Lichtner, Peter

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AU - Lunetta, Kathryn L.

AU - Lubitz, Steven A.

AU - Ellinor, Patrick T.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

AB - Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

UR - http://www.scopus.com/inward/record.url?scp=85017510399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017510399&partnerID=8YFLogxK

U2 - 10.1038/ng.3843

DO - 10.1038/ng.3843

M3 - Article

C2 - 28416818

AN - SCOPUS:85017510399

VL - 49

SP - 946

EP - 952

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 6

ER -