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 Mueller-Nurasyid, J. Gustav Smith, Jennifer A. Brody & 142 others Maartje N. Niemeijer, Marcus Doerr, Stella Trompet, Jennifer E. Huffman, Stefan Gustafsson, Claudia Schurmann, Marcus E. Kleber, Leo-Pekka Lyytikainen, Ilkka Seppala, Rainer Malik, Andrea R. V. R. Horimoto, Marco Perez, Juha Sinisalo, Stefanie Aeschbacher, Sebastien Theriault, 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 Pare, 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 Kahonen, 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. E. Magnusson, David J. 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 M. 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 Voelker, Karl-Heinz Joeckel, 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 Maerz, Terho Lehtimaki, Bruno H. C. Stricker, Mina K. Chung, Stephan B. Felix, Vilmundur Gudnason, Alvaro Alonso, Dan M. Roden, Stefan Kaeaeb, Daniel I. Chasman, Susan R. Heckbert, Emelia J. Benjamin, Toshihiro Tanaka, Kathryn L. Lunetta, Steven A. Lubitz, Patrick T. Ellinor

    Research output: Contribution to journalLetter

    61 Citations (Scopus)
    48 Downloads (Pure)

    Abstract

    Atrial fibrillation (AF) affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with AF in European and Asian ancestry groups.3–7 To further define the genetic basis of AF, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with AF and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel 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 AF, provide insights into the molecular basis of AF, and may facilitate new potential targets for drug discovery.
    Original languageEnglish
    Pages (from-to)946-952
    Number of pages7
    JournalNature Genetics
    Volume49
    Issue number6
    Early online date17 Apr 2017
    DOIs
    Publication statusPublished - Jun 2017

    Keywords

    • Atrial fibrillation
    • population genetics
    • genome-wide association studies
    • gene expression

    Cite this

    Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., ... 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. ; Mueller-Nurasyid, Martina ; Smith, J. Gustav ; Brody, Jennifer A. ; Niemeijer, Maartje N. ; Doerr, Marcus ; Trompet, Stella ; Huffman, Jennifer E. ; Gustafsson, Stefan ; Schurmann, Claudia ; Kleber, Marcus E. ; Lyytikainen, Leo-Pekka ; Seppala, Ilkka ; Malik, Rainer ; Horimoto, Andrea R. V. R. ; Perez, Marco ; Sinisalo, Juha ; Aeschbacher, Stefanie ; Theriault, Sebastien ; 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. ; Pare, 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. ; Kahonen, 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. E. ; Porteous, David J. ; 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 M. ; Macfarlane, Peter W ; Heilmann-Heimbach, Stefanie ; Almgren, Peter ; Huang, Paul L. ; Sotoodehnia, Nona ; Soliman, Elsayed Z. ; Uitterlinden, Andre G. ; Hofman, Albert ; Franco, Oscar H. ; Voelker, Uwe ; Joeckel, 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. ; Maerz, Winfried ; Lehtimaki, Terho ; Stricker, Bruno H. C. ; Chung, Mina K. ; Felix, Stephan B. ; Gudnason, Vilmundur ; Alonso, Alvaro ; Roden, Dan M. ; Kaeaeb, 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.
    @article{44416dc5bef042d7b20d1a47862e903a,
    title = "Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation",
    abstract = "Atrial fibrillation (AF) affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with AF in European and Asian ancestry groups.3–7 To further define the genetic basis of AF, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with AF and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel 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 AF, provide insights into the molecular basis of AF, and may facilitate new potential targets for drug discovery.",
    keywords = "Atrial fibrillation, population genetics, genome-wide association studies, gene expression",
    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 Siew-Kee Low and Weeke, {Peter E.} and Martina Mueller-Nurasyid and Smith, {J. Gustav} and Brody, {Jennifer A.} and Niemeijer, {Maartje N.} and Marcus Doerr and Stella Trompet and Huffman, {Jennifer E.} and Stefan Gustafsson and Claudia Schurmann and Kleber, {Marcus E.} and Leo-Pekka Lyytikainen and Ilkka Seppala and Rainer Malik and Horimoto, {Andrea R. V. R.} and Marco Perez and Juha Sinisalo and Stefanie Aeschbacher and Sebastien Theriault and Jie Yao and Farid Radmanesh and Stefan Weiss and Alexander Teumer and Choi, {Seung Hoan} and Lu-Chen Weng 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 Pare 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 Kahonen 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. E.} and Porteous, {David J.} 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 Shaffer, {Christian M.} 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 Voelker and Karl-Heinz Joeckel 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 Marja-Liisa Lokki and Sekar Kathiresan and Alexandre Pereira and Jukema, {J. Wouter} and Caroline Hayward and Rotter, {Jerome I.} and Winfried Maerz and Terho Lehtimaki and Stricker, {Bruno H. C.} and Chung, {Mina K.} and Felix, {Stephan B.} and Vilmundur Gudnason and Alvaro Alonso and Roden, {Dan M.} and Stefan Kaeaeb 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.}",
    note = "Full list of funding on supplementary data page.",
    year = "2017",
    month = "6",
    doi = "10.1038/ng.3843",
    language = "English",
    volume = "49",
    pages = "946--952",
    journal = "Nature Genetics",
    issn = "1061-4036",
    publisher = "Nature Publishing Group",
    number = "6",

    }

    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, S-K, Weeke, PE, Mueller-Nurasyid, M, Smith, JG, Brody, JA, Niemeijer, MN, Doerr, M, Trompet, S, Huffman, JE, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikainen, L-P, Seppala, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Theriault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Choi, SH, Weng, L-C, Clauss, S, Deo, R, Rader, DJ, Shah, SH, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Pare, 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, Kahonen, 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, Y-DI, Sandhu, RK, Li, M, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Anderson, CD, Taylor, KD, Campbell, A, Magnusson, PKE, Porteous, DJ, 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, CM, Macfarlane, PW, Heilmann-Heimbach, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Voelker, U, Joeckel, K-H, 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, M-L, Kathiresan, S, Pereira, A, Jukema, JW, Hayward, C, Rotter, JI, Maerz, W, Lehtimaki, T, Stricker, BHC, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kaeaeb, 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.; Mueller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Doerr, Marcus; Trompet, Stella; Huffman, Jennifer E.; Gustafsson, Stefan; Schurmann, Claudia; Kleber, Marcus E.; Lyytikainen, Leo-Pekka; Seppala, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Theriault, Sebastien; 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.; Pare, 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.; Kahonen, 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. E.; Porteous, David J.; 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 M.; Macfarlane, Peter W; Heilmann-Heimbach, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Voelker, Uwe; Joeckel, 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.; Maerz, Winfried; Lehtimaki, Terho; Stricker, Bruno H. C.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kaeaeb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T. (Lead / Corresponding author).

    In: Nature Genetics, Vol. 49, No. 6, 06.2017, p. 946-952.

    Research output: Contribution to journalLetter

    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 - Mueller-Nurasyid, Martina

    AU - Smith, J. Gustav

    AU - Brody, Jennifer A.

    AU - Niemeijer, Maartje N.

    AU - Doerr, Marcus

    AU - Trompet, Stella

    AU - Huffman, Jennifer E.

    AU - Gustafsson, Stefan

    AU - Schurmann, Claudia

    AU - Kleber, Marcus E.

    AU - Lyytikainen, Leo-Pekka

    AU - Seppala, Ilkka

    AU - Malik, Rainer

    AU - Horimoto, Andrea R. V. R.

    AU - Perez, Marco

    AU - Sinisalo, Juha

    AU - Aeschbacher, Stefanie

    AU - Theriault, Sebastien

    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 - Pare, 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

    AU - Arendt, Marina

    AU - Krieger, Jose E.

    AU - Kahonen, Mika

    AU - Risch, Lorenz

    AU - Mansur, Alfredo J.

    AU - Peters, Annette

    AU - Smith, Blair H.

    AU - Lind, Lars

    AU - Scott, Stuart A.

    AU - Lu, Yingchang

    AU - Bottinger, Erwin B.

    AU - Hernesniemi, Jussi

    AU - Lindgren, Cecilia M.

    AU - Wong, Jorge A.

    AU - Huang, Jie

    AU - Eskola, Markku

    AU - Morris, Andrew P.

    AU - Ford, Ian

    AU - Reiner, Alex P.

    AU - Delgado, Graciela

    AU - Chen, Lin Y.

    AU - Chen, Yii-Der Ida

    AU - Sandhu, Roopinder K.

    AU - Li, Man

    AU - Boerwinkle, Eric

    AU - Eisele, Lewin

    AU - Lannfelt, Lars

    AU - Rost, Natalia

    AU - Anderson, Christopher D.

    AU - Taylor, Kent D.

    AU - Campbell, Archie

    AU - Magnusson, Patrik K. E.

    AU - Porteous, David J.

    AU - Hocking, Lynne J.

    AU - Vlachopoulou, Efthymia

    AU - Pedersen, Nancy L.

    AU - Nikus, Kjell

    AU - Orho-Melander, Marju

    AU - Hamsten, Anders

    AU - Heeringa, Jan

    AU - Denny, Joshua C.

    AU - Kriebel, Jennifer

    AU - Darbar, Dawood

    AU - Newton-Cheh, Christopher

    AU - Shaffer, Christian M.

    AU - Macfarlane, Peter W

    AU - Heilmann-Heimbach, Stefanie

    AU - Almgren, Peter

    AU - Huang, Paul L.

    AU - Sotoodehnia, Nona

    AU - Soliman, Elsayed Z.

    AU - Uitterlinden, Andre G.

    AU - Hofman, Albert

    AU - Franco, Oscar H.

    AU - Voelker, Uwe

    AU - Joeckel, Karl-Heinz

    AU - Sinner, Moritz F.

    AU - Lin, Henry J

    AU - Guo, Xiuqing

    AU - Dichgans, Martin

    AU - Ingelsson, Erik

    AU - Kooperberg, Charles

    AU - Melander, Olle

    AU - Loos, Ruth J. F.

    AU - Laurikka, Jari

    AU - Conen, David

    AU - Rosand, Jonathan

    AU - van der Harst, Pim

    AU - Lokki, Marja-Liisa

    AU - Kathiresan, Sekar

    AU - Pereira, Alexandre

    AU - Jukema, J. Wouter

    AU - Hayward, Caroline

    AU - Rotter, Jerome I.

    AU - Maerz, Winfried

    AU - Lehtimaki, Terho

    AU - Stricker, Bruno H. C.

    AU - Chung, Mina K.

    AU - Felix, Stephan B.

    AU - Gudnason, Vilmundur

    AU - Alonso, Alvaro

    AU - Roden, Dan M.

    AU - Kaeaeb, Stefan

    AU - Chasman, Daniel I.

    AU - Heckbert, Susan R.

    AU - Benjamin, Emelia J.

    AU - Tanaka, Toshihiro

    AU - Lunetta, Kathryn L.

    AU - Lubitz, Steven A.

    AU - Ellinor, Patrick T.

    N1 - Full list of funding on supplementary data page.

    PY - 2017/6

    Y1 - 2017/6

    N2 - Atrial fibrillation (AF) affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with AF in European and Asian ancestry groups.3–7 To further define the genetic basis of AF, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with AF and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel 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 AF, provide insights into the molecular basis of AF, and may facilitate new potential targets for drug discovery.

    AB - Atrial fibrillation (AF) affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with AF in European and Asian ancestry groups.3–7 To further define the genetic basis of AF, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with AF and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel 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 AF, provide insights into the molecular basis of AF, and may facilitate new potential targets for drug discovery.

    KW - Atrial fibrillation

    KW - population genetics

    KW - genome-wide association studies

    KW - gene expression

    U2 - 10.1038/ng.3843

    DO - 10.1038/ng.3843

    M3 - Letter

    VL - 49

    SP - 946

    EP - 952

    JO - Nature Genetics

    JF - Nature Genetics

    SN - 1061-4036

    IS - 6

    ER -

    Christophersen IE, Rienstra M, Roselli C, Yin X, Geelhoed B, Barnard J et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nature Genetics. 2017 Jun;49(6):946-952. https://doi.org/10.1038/ng.3843