Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Patrick T. Ellinor, Kathryn L. Lunetta, Christine M. Albert, Nicole L. Glazer, Marylyn D. Ritchie, Albert V. Smith, Dan E. Arking, Martina Müller-Nurasyid, Bouwe P. Krijthe, Steven A. Lubitz, Joshua C. Bis, Mina K. Chung, Marcus Dörr, Kouichi Ozaki, Jason D. Roberts, J. Gustav Smith, Arne Pfeufer, Moritz F. Sinner, Kurt Lohman, Jingzhong DingNicholas L. Smith, Jonathan D. Smith, Michiel Rienstra, Kenneth M. Rice, David R. Van Wagoner, Jared W. Magnani, Reza Wakili, Sebastian Clauss, Jerome I. Rotter, Gerhard Steinbeck, Lenore J. Launer, Robert W. Davies, Matthew Borkovich, Tamara B. Harris, Honghuang Lin, Uwe Völker, Henry Völzke, David J. Milan, Albert Hofman, Eric Boerwinkle, Lin Y. Chen, Elsayed Z. Soliman, Benjamin F. Voight, Guo Li, Aravinda Chakravarti, Michiaki Kubo, Usha B. Tedrow, Lynda M. Rose, Paul M. Ridker, David Conen, Tatsuhiko Tsunoda, Tetsushi Furukawa, Nona Sotoodehnia, Siyan Xu, Naoyuki Kamatani, Daniel Levy, Yusuke Nakamura, Babar Parvez, Saagar Mahida, Karen L. Furie, Jonathan Rosand, Raafia Muhammad, Bruce M. Psaty, Thomas Meitinger, Siegfried Perz, H. Erich Wichmann, Jacqueline C.M. Witteman, W. H.Linda Kao, Sekar Kathiresan, Dan M. Roden, Andre G. Uitterlinden, Fernando Rivadeneira, Barbara McKnight, Marketa Sjögren, Anne B. Newman, Yongmei Liu, Michael H. Gollob, Olle Melander, Toshihiro Tanaka, Bruno H.Ch Stricker, Stephan B. Felix, Alvaro Alonso, Dawood Darbar, John Barnard, Daniel I. Chasman, Susan R. Heckbert, Emelia J. Benjamin, Vilmundur Gudnason, Stefan Kääb

Research output: Contribution to journalArticle

344 Citations (Scopus)

Abstract

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10-8). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

Original languageEnglish
Pages (from-to)670-675
Number of pages6
JournalNature Genetics
Volume44
Issue number6
DOIs
Publication statusPublished - 01-06-2012

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Atrial Fibrillation
Meta-Analysis
Genome-Wide Association Study
Ion Channels
Computer Simulation
Cardiac Arrhythmias
Transcription Factors
Heart Failure
Stroke
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Ellinor, P. T., Lunetta, K. L., Albert, C. M., Glazer, N. L., Ritchie, M. D., Smith, A. V., ... Kääb, S. (2012). Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nature Genetics, 44(6), 670-675. https://doi.org/10.1038/ng.2261
Ellinor, Patrick T. ; Lunetta, Kathryn L. ; Albert, Christine M. ; Glazer, Nicole L. ; Ritchie, Marylyn D. ; Smith, Albert V. ; Arking, Dan E. ; Müller-Nurasyid, Martina ; Krijthe, Bouwe P. ; Lubitz, Steven A. ; Bis, Joshua C. ; Chung, Mina K. ; Dörr, Marcus ; Ozaki, Kouichi ; Roberts, Jason D. ; Smith, J. Gustav ; Pfeufer, Arne ; Sinner, Moritz F. ; Lohman, Kurt ; Ding, Jingzhong ; Smith, Nicholas L. ; Smith, Jonathan D. ; Rienstra, Michiel ; Rice, Kenneth M. ; Van Wagoner, David R. ; Magnani, Jared W. ; Wakili, Reza ; Clauss, Sebastian ; Rotter, Jerome I. ; Steinbeck, Gerhard ; Launer, Lenore J. ; Davies, Robert W. ; Borkovich, Matthew ; Harris, Tamara B. ; Lin, Honghuang ; Völker, Uwe ; Völzke, Henry ; Milan, David J. ; Hofman, Albert ; Boerwinkle, Eric ; Chen, Lin Y. ; Soliman, Elsayed Z. ; Voight, Benjamin F. ; Li, Guo ; Chakravarti, Aravinda ; Kubo, Michiaki ; Tedrow, Usha B. ; Rose, Lynda M. ; Ridker, Paul M. ; Conen, David ; Tsunoda, Tatsuhiko ; Furukawa, Tetsushi ; Sotoodehnia, Nona ; Xu, Siyan ; Kamatani, Naoyuki ; Levy, Daniel ; Nakamura, Yusuke ; Parvez, Babar ; Mahida, Saagar ; Furie, Karen L. ; Rosand, Jonathan ; Muhammad, Raafia ; Psaty, Bruce M. ; Meitinger, Thomas ; Perz, Siegfried ; Wichmann, H. Erich ; Witteman, Jacqueline C.M. ; Kao, W. H.Linda ; Kathiresan, Sekar ; Roden, Dan M. ; Uitterlinden, Andre G. ; Rivadeneira, Fernando ; McKnight, Barbara ; Sjögren, Marketa ; Newman, Anne B. ; Liu, Yongmei ; Gollob, Michael H. ; Melander, Olle ; Tanaka, Toshihiro ; Stricker, Bruno H.Ch ; Felix, Stephan B. ; Alonso, Alvaro ; Darbar, Dawood ; Barnard, John ; Chasman, Daniel I. ; Heckbert, Susan R. ; Benjamin, Emelia J. ; Gudnason, Vilmundur ; Kääb, Stefan. / Meta-analysis identifies six new susceptibility loci for atrial fibrillation. In: Nature Genetics. 2012 ; Vol. 44, No. 6. pp. 670-675.
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Ellinor, PT, Lunetta, KL, Albert, CM, Glazer, NL, Ritchie, MD, Smith, AV, Arking, DE, Müller-Nurasyid, M, Krijthe, BP, Lubitz, SA, Bis, JC, Chung, MK, Dörr, M, Ozaki, K, Roberts, JD, Smith, JG, Pfeufer, A, Sinner, MF, Lohman, K, Ding, J, Smith, NL, Smith, JD, Rienstra, M, Rice, KM, Van Wagoner, DR, Magnani, JW, Wakili, R, Clauss, S, Rotter, JI, Steinbeck, G, Launer, LJ, Davies, RW, Borkovich, M, Harris, TB, Lin, H, Völker, U, Völzke, H, Milan, DJ, Hofman, A, Boerwinkle, E, Chen, LY, Soliman, EZ, Voight, BF, Li, G, Chakravarti, A, Kubo, M, Tedrow, UB, Rose, LM, Ridker, PM, Conen, D, Tsunoda, T, Furukawa, T, Sotoodehnia, N, Xu, S, Kamatani, N, Levy, D, Nakamura, Y, Parvez, B, Mahida, S, Furie, KL, Rosand, J, Muhammad, R, Psaty, BM, Meitinger, T, Perz, S, Wichmann, HE, Witteman, JCM, Kao, WHL, Kathiresan, S, Roden, DM, Uitterlinden, AG, Rivadeneira, F, McKnight, B, Sjögren, M, Newman, AB, Liu, Y, Gollob, MH, Melander, O, Tanaka, T, Stricker, BHC, Felix, SB, Alonso, A, Darbar, D, Barnard, J, Chasman, DI, Heckbert, SR, Benjamin, EJ, Gudnason, V & Kääb, S 2012, 'Meta-analysis identifies six new susceptibility loci for atrial fibrillation', Nature Genetics, vol. 44, no. 6, pp. 670-675. https://doi.org/10.1038/ng.2261

Meta-analysis identifies six new susceptibility loci for atrial fibrillation. / Ellinor, Patrick T.; Lunetta, Kathryn L.; Albert, Christine M.; Glazer, Nicole L.; Ritchie, Marylyn D.; Smith, Albert V.; Arking, Dan E.; Müller-Nurasyid, Martina; Krijthe, Bouwe P.; Lubitz, Steven A.; Bis, Joshua C.; Chung, Mina K.; Dörr, Marcus; Ozaki, Kouichi; Roberts, Jason D.; Smith, J. Gustav; Pfeufer, Arne; Sinner, Moritz F.; Lohman, Kurt; Ding, Jingzhong; Smith, Nicholas L.; Smith, Jonathan D.; Rienstra, Michiel; Rice, Kenneth M.; Van Wagoner, David R.; Magnani, Jared W.; Wakili, Reza; Clauss, Sebastian; Rotter, Jerome I.; Steinbeck, Gerhard; Launer, Lenore J.; Davies, Robert W.; Borkovich, Matthew; Harris, Tamara B.; Lin, Honghuang; Völker, Uwe; Völzke, Henry; Milan, David J.; Hofman, Albert; Boerwinkle, Eric; Chen, Lin Y.; Soliman, Elsayed Z.; Voight, Benjamin F.; Li, Guo; Chakravarti, Aravinda; Kubo, Michiaki; Tedrow, Usha B.; Rose, Lynda M.; Ridker, Paul M.; Conen, David; Tsunoda, Tatsuhiko; Furukawa, Tetsushi; Sotoodehnia, Nona; Xu, Siyan; Kamatani, Naoyuki; Levy, Daniel; Nakamura, Yusuke; Parvez, Babar; Mahida, Saagar; Furie, Karen L.; Rosand, Jonathan; Muhammad, Raafia; Psaty, Bruce M.; Meitinger, Thomas; Perz, Siegfried; Wichmann, H. Erich; Witteman, Jacqueline C.M.; Kao, W. H.Linda; Kathiresan, Sekar; Roden, Dan M.; Uitterlinden, Andre G.; Rivadeneira, Fernando; McKnight, Barbara; Sjögren, Marketa; Newman, Anne B.; Liu, Yongmei; Gollob, Michael H.; Melander, Olle; Tanaka, Toshihiro; Stricker, Bruno H.Ch; Felix, Stephan B.; Alonso, Alvaro; Darbar, Dawood; Barnard, John; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Gudnason, Vilmundur; Kääb, Stefan.

In: Nature Genetics, Vol. 44, No. 6, 01.06.2012, p. 670-675.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Meta-analysis identifies six new susceptibility loci for atrial fibrillation

AU - Ellinor, Patrick T.

AU - Lunetta, Kathryn L.

AU - Albert, Christine M.

AU - Glazer, Nicole L.

AU - Ritchie, Marylyn D.

AU - Smith, Albert V.

AU - Arking, Dan E.

AU - Müller-Nurasyid, Martina

AU - Krijthe, Bouwe P.

AU - Lubitz, Steven A.

AU - Bis, Joshua C.

AU - Chung, Mina K.

AU - Dörr, Marcus

AU - Ozaki, Kouichi

AU - Roberts, Jason D.

AU - Smith, J. Gustav

AU - Pfeufer, Arne

AU - Sinner, Moritz F.

AU - Lohman, Kurt

AU - Ding, Jingzhong

AU - Smith, Nicholas L.

AU - Smith, Jonathan D.

AU - Rienstra, Michiel

AU - Rice, Kenneth M.

AU - Van Wagoner, David R.

AU - Magnani, Jared W.

AU - Wakili, Reza

AU - Clauss, Sebastian

AU - Rotter, Jerome I.

AU - Steinbeck, Gerhard

AU - Launer, Lenore J.

AU - Davies, Robert W.

AU - Borkovich, Matthew

AU - Harris, Tamara B.

AU - Lin, Honghuang

AU - Völker, Uwe

AU - Völzke, Henry

AU - Milan, David J.

AU - Hofman, Albert

AU - Boerwinkle, Eric

AU - Chen, Lin Y.

AU - Soliman, Elsayed Z.

AU - Voight, Benjamin F.

AU - Li, Guo

AU - Chakravarti, Aravinda

AU - Kubo, Michiaki

AU - Tedrow, Usha B.

AU - Rose, Lynda M.

AU - Ridker, Paul M.

AU - Conen, David

AU - Tsunoda, Tatsuhiko

AU - Furukawa, Tetsushi

AU - Sotoodehnia, Nona

AU - Xu, Siyan

AU - Kamatani, Naoyuki

AU - Levy, Daniel

AU - Nakamura, Yusuke

AU - Parvez, Babar

AU - Mahida, Saagar

AU - Furie, Karen L.

AU - Rosand, Jonathan

AU - Muhammad, Raafia

AU - Psaty, Bruce M.

AU - Meitinger, Thomas

AU - Perz, Siegfried

AU - Wichmann, H. Erich

AU - Witteman, Jacqueline C.M.

AU - Kao, W. H.Linda

AU - Kathiresan, Sekar

AU - Roden, Dan M.

AU - Uitterlinden, Andre G.

AU - Rivadeneira, Fernando

AU - McKnight, Barbara

AU - Sjögren, Marketa

AU - Newman, Anne B.

AU - Liu, Yongmei

AU - Gollob, Michael H.

AU - Melander, Olle

AU - Tanaka, Toshihiro

AU - Stricker, Bruno H.Ch

AU - Felix, Stephan B.

AU - Alonso, Alvaro

AU - Darbar, Dawood

AU - Barnard, John

AU - Chasman, Daniel I.

AU - Heckbert, Susan R.

AU - Benjamin, Emelia J.

AU - Gudnason, Vilmundur

AU - Kääb, Stefan

PY - 2012/6/1

Y1 - 2012/6/1

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AB - Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10-8). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

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Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nature Genetics. 2012 Jun 1;44(6):670-675. https://doi.org/10.1038/ng.2261