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

Ingrid E., Christophersen, The Broad Institute of MIT and Harvard; Michiel, Rienstra, University of Groningen; Carolina, Roselli, The Broad Institute of MIT and Harvard; Xiaoyan, Yin, NHLBI and Boston University’s Framingham Heart Study; Bastiaan, Geelhoed, University of Groningen; John, Barnard, Cleveland Clinic; Honghuang, Lin, NHLBI and Boston University’s Framingham Heart Study; Dan E., Arking, Johns Hopkins University School of Medicine; Albert V., Smith, Icelandic Heart Association; Christine M., Albert, Harvard Medical School; Mark, Chaffin, The Broad Institute of MIT and Harvard; Nathan R., Tucker, The Broad Institute of MIT and Harvard; Molong, Li, Massachusetts General Hospital; Derek, Klarin, The Broad Institute of MIT and Harvard; Nathan A., Bihlmeyer, Johns Hopkins University School of Medicine; Siew-Kee, Low, RIKEN Center for Integrative Medical Sciences; Peter E., Weeke, Vanderbilt University; Martina, Mueller-Nurasyid, Helmholtz Zentrum München – German Research Center for Environmental Health; J. Gustav, Smith, The Broad Institute of MIT and Harvard; Jennifer A., Brody, University of Washington; Maartje N., Niemeijer, Erasmus University Medical Center Rotterdam; Marcus, Doerr, University Medicine Greifswald; Stella, Trompet, Leiden University; Jennifer, Huffman, University of Edinburgh; Stefan, Gustafsson, Uppsala University; Claudia, Schurmann, Icahn School of Medicine at Mount Sinai; Marcus E., Kleber, Heidelberg University; Leo-Pekka, Lyytikainen, Fimlab Laboratories and University of Tampere School of Medicine; Ilkka, Seppala, Fimlab Laboratories and University of Tampere School of Medicine; Rainer, Malik, Klinikum der Universität München; Andrea R. V. R., Horimoto, University of Sao Paulo; Marco, Perez, Stanford University; Juha, Sinisalo, Helsinki University Central Hospital; Stefanie, Aeschbacher, University Hospital Basel; Sebastien, Theriault, Population Health Research Institute; Jie, Yao, Harbor-UCLA Medical Center; Farid, Radmanesh, The Broad Institute of MIT and Harvard; Stefan, Weiss, DZHK (German Centre for Cardiovascular Research), partner site Greifswald; Alexander, Teumer, DZHK (German Centre for Cardiovascular Research), partner site Greifswald; Seung Hoan, Choi, The Broad Institute of MIT and Harvard; Lu-Chen, Weng, The Broad Institute of MIT and Harvard; Sebastien, Clauss, Massachusetts General Hospital; Rajat, Deo, University of Pennsylvania; Daniel J., Rader, University of Pennsylvania; Svati, Shah, Duke University; Albert, Sun, Duke University; Jemma C., Hopewell, University of Oxford; Stephanie, Debette, Inserm Center U1219 (Bordeaux Population Health Centre); Ganesh, Chauhan, Inserm Center U1219 (Bordeaux Population Health Centre); Qiong, Yang, Boston University; Bradford B., Worrall, University of Virginia Health System; Guillaume, Pare, Population Health Research Institute; Yoichiro, Kamatani, RIKEN Center for Integrative Medical Sciences; Yanick P., Hagemeijer, University of Groningen; Niek, Verweij, University of Groningen; Joylene E., Siland, University of Groningen; Michiaki, Kubo, RIKEN Center for Integrative Medical Sciences; Jonathan D., Smith, Cleveland Clinic; David R., Van Wagoner, Cleveland Clinic; Joshua C., Bis, University of Washington; Siegfried, Perz, Helmholtz Zentrum München – German Research Center for Environmental Health; Bruce M., Psaty, University of Washington; Paul M., Ridker, Harvard Medical School; Jared W., Magnani, NHLBI and Boston University’s Framingham Heart Study; Tamara B., Harris, National Institute on Aging; Lenore J., Launer, National Institute on Aging; M. Benjamin, Shoemaker, Vanderbilt University; Sandosh, Padmanabhan, University of Glasgow; Jeffrey, Haessler, University of Washington; Traci M., Bartz, University of Washington; Melanie, Waldenberger, DZHK (German Centre for Cardiovascular Research), partner site Greifswald; Peter, Lichtner, Helmholtz Zentrum München – German Research Center for Environmental Health; Marina, Arendt, University Duisburg-Essen; Jose E., Krieger, University of Sao Paulo; Mika, Kahonen, University of Tampere; Lorenz, Risch, University of Bern; Alfredo J., Mansur, University of Sao Paulo; Annette, Peters, DZHK (German Centre for Cardiovascular Research), partner site Greifswald; Blair H., Smith, University of Dundee; Lars, Lind, Uppsala University; Stuart A., Scott, Icahn School of Medicine at Mount Sinai; Yingchang, Lu, Icahn School of Medicine at Mount Sinai; Erwin B., Bottinger, Icahn School of Medicine at Mount Sinai; Jussi, Hernesniemi, Fimlab Laboratories and University of Tampere School of Medicine; Cecilia M., Lindgren, University of Oxford; Jorje, Wong, McMaster University; Jie, Huang, Boston VA Research Institute; Markku, Eskola, University of Tampere; Andrew P., Morris, University of Oxford; Ian, Ford, University of Glasgow; Alex P., Reiner, University of Washington; Graciela, Delgado, Heidelberg University; Lin Y., Chen, University of Minnesota; Yii-Der Ida, Chen, Harbor-UCLA Medical Center; Roopinder K., Sandhu, University of Alberta; Man, Li, Massachusetts General Hospital; Eric, Boerwinkle, Baylor College of Medicine; Lewin, Eisele, University Duisburg-Essen; Lars, Lannfelt, Uppsala University; Natalia, Rost, The Broad Institute of MIT and Harvard; Christopher D., Anderson, The Broad Institute of MIT and Harvard; Kent D., Taylor, Harbor-UCLA Medical Center; Archie, Campbell, University of Edinburgh; Patrik K., Magnusson, Karolinska Institutet; David, Porteous, University of Edinburgh; Lynne J., Hocking, University of Aberdeen; Efthymia, Vlachopoulou, University of Helsinki; Nancy L., Pedersen, Karolinska Institutet; Kjell, Nikus, University of Tampere; Marju, Orho-Melander, Lund University; Anders, Hamsten, Karolinska Institutet; Jan, Heeringa, Erasmus University Medical Center Rotterdam; Joshua C, Denny, Vanderbilt University; Jennifer, Kriebel, Helmholtz Zentrum Munchen German Res Ctr Environm; Dawood, Darbar, University of Illinois; Christopher, Newton-Cheh, The Broad Institute of MIT and Harvard; Christian, Shaffer, Vanderbilt University; Peter W., Macfarlane, University of Glasgow; Stefanie, Heilmann-Heimbach, University of Bonn; Peter, Almgren, Lund University; Paul L., Huang, The Broad Institute of MIT and Harvard; Nona, Sotoodehnia, University of Washington; Elsayed Z., Soliman, Wake Forest School of Medicine; Andre G., Uitterlinden, Erasmus University Medical Center Rotterdam; Albert, Hofman, Erasmus University Medical Center Rotterdam; Oscar H., Franco, Erasmus University Medical Center Rotterdam; Uwe, Voelker, DZHK (German Centre for Cardiovascular Research); Karl-Heinz, Joeckel, University Duisburg-Essen; Moritz F., Sinner, University Hospital Munich; Henry J., Lin, Harbor-UCLA Medical Center; Xiuqing, Guo, Harbor-UCLA Medical Center; Martin, Dichgans, Klinikum der Universität München; Erik, Ingelsson, Uppsala University; Charles, Kooperberg, University of Washington; Olle, Melander, Lund University; Ruth J. F., Loos, Icahn School of Medicine at Mount Sinai; Jari, Laurikka, University of Tampere; David, Conen, University Hospital Basel; Jonathan, Rosand, The Broad Institute of MIT and Harvard; Pim, van der Harst, University of Groningen; Marja-Liisa, Lokki, University of Helsinki; Sekar, Kathiresan, The Broad Institute of MIT and Harvard; Alexandre, Pereira, University of Sao Paulo; J. Wouter, Jukema, Leiden University; Caroline, Hayward, University of Edinburgh; Jerome I., Rotter, Harbor-UCLA Medical Center; Winfried, Maerz, Medical University of Graz; Terho, Lehtimaki, Fimlab Laboratories and University of Tampere School of Medicine; Bruno H., Stricker, Erasmus University Medical Center Rotterdam; Mina K., Chung, Cleveland Clinic; Stephan B., Felix, University Medicine Greifswald; Vilmundur, Gudnason, Icelandic Heart Association; Alvaro, Alonso, Emory University; Dan M., Roden, Vanderbilt University; Stefan, Kaeaeb, University Hospital Munich; Daniel I., Chasman, The Broad Institute of MIT and Harvard; Susan R., Heckbert, University of Washington; Emelia J., Benjamin, NHLBI and Boston University’s Framingham Heart Study; Toshihiro, Tanaka, RIKEN Center for Integrative Medical Sciences; Kathryn L., Lunetta, NHLBI and Boston University’s Framingham Heart Study; Steven A., Lubitz, The Broad Institute of MIT and Harvard; Patrick T., Ellinor, The Broad Institute of MIT and Harvard

Publication

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

Persistent URL

https://open.library.emory.edu/purl/2322bvq8f9-emory

Last modified

05/21/2025

Type of Material

Article

Authors

Ingrid E. Christophersen, The Broad Institute of MIT and Harvard

Michiel Rienstra, University of Groningen

Carolina Roselli, The Broad Institute of MIT and Harvard

Xiaoyan Yin, NHLBI and Boston University’s Framingham Heart Study

Bastiaan Geelhoed, University of Groningen

John Barnard, Cleveland ClinicHonghuang Lin, NHLBI and Boston University’s Framingham Heart StudyDan E. Arking, Johns Hopkins University School of MedicineAlbert V. Smith, Icelandic Heart AssociationChristine M. Albert, Harvard Medical SchoolMark Chaffin, The Broad Institute of MIT and HarvardNathan R. Tucker, The Broad Institute of MIT and HarvardMolong Li, Massachusetts General HospitalDerek Klarin, The Broad Institute of MIT and HarvardNathan A. Bihlmeyer, Johns Hopkins University School of MedicineSiew-Kee Low, RIKEN Center for Integrative Medical SciencesPeter E. Weeke, Vanderbilt UniversityMartina Mueller-Nurasyid, Helmholtz Zentrum München – German Research Center for Environmental HealthJ. Gustav Smith, The Broad Institute of MIT and HarvardJennifer A. Brody, University of WashingtonMaartje N. Niemeijer, Erasmus University Medical Center RotterdamMarcus Doerr, University Medicine GreifswaldStella Trompet, Leiden UniversityJennifer Huffman, University of EdinburghStefan Gustafsson, Uppsala UniversityClaudia Schurmann, Icahn School of Medicine at Mount SinaiMarcus E. Kleber, Heidelberg UniversityLeo-Pekka Lyytikainen, Fimlab Laboratories and University of Tampere School of MedicineIlkka Seppala, Fimlab Laboratories and University of Tampere School of MedicineRainer Malik, Klinikum der Universität MünchenAndrea R. V. R. Horimoto, University of Sao PauloMarco Perez, Stanford UniversityJuha Sinisalo, Helsinki University Central HospitalStefanie Aeschbacher, University Hospital BaselSebastien Theriault, Population Health Research InstituteJie Yao, Harbor-UCLA Medical CenterFarid Radmanesh, The Broad Institute of MIT and HarvardStefan Weiss, DZHK (German Centre for Cardiovascular Research), partner site GreifswaldAlexander Teumer, DZHK (German Centre for Cardiovascular Research), partner site GreifswaldSeung Hoan Choi, The Broad Institute of MIT and HarvardLu-Chen Weng, The Broad Institute of MIT and HarvardSebastien Clauss, Massachusetts General HospitalRajat Deo, University of PennsylvaniaDaniel J. Rader, University of PennsylvaniaSvati Shah, Duke UniversityAlbert Sun, Duke UniversityJemma C. Hopewell, University of OxfordStephanie Debette, Inserm Center U1219 (Bordeaux Population Health Centre)Ganesh Chauhan, Inserm Center U1219 (Bordeaux Population Health Centre)Qiong Yang, Boston UniversityBradford B. Worrall, University of Virginia Health SystemGuillaume Pare, Population Health Research InstituteYoichiro Kamatani, RIKEN Center for Integrative Medical SciencesYanick P. Hagemeijer, University of GroningenNiek Verweij, University of GroningenJoylene E. Siland, University of GroningenMichiaki Kubo, RIKEN Center for Integrative Medical SciencesJonathan D. Smith, Cleveland ClinicDavid R. Van Wagoner, Cleveland ClinicJoshua C. Bis, University of WashingtonSiegfried Perz, Helmholtz Zentrum München – German Research Center for Environmental HealthBruce M. Psaty, University of WashingtonPaul M. Ridker, Harvard Medical SchoolJared W. Magnani, NHLBI and Boston University’s Framingham Heart StudyTamara B. Harris, National Institute on AgingLenore J. Launer, National Institute on AgingM. Benjamin Shoemaker, Vanderbilt UniversitySandosh Padmanabhan, University of GlasgowJeffrey Haessler, University of WashingtonTraci M. Bartz, University of WashingtonMelanie Waldenberger, DZHK (German Centre for Cardiovascular Research), partner site GreifswaldPeter Lichtner, Helmholtz Zentrum München – German Research Center for Environmental HealthMarina Arendt, University Duisburg-EssenJose E. Krieger, University of Sao PauloMika Kahonen, University of TampereLorenz Risch, University of BernAlfredo J. Mansur, University of Sao PauloAnnette Peters, DZHK (German Centre for Cardiovascular Research), partner site GreifswaldBlair H. Smith, University of DundeeLars Lind, Uppsala UniversityStuart A. Scott, Icahn School of Medicine at Mount SinaiYingchang Lu, Icahn School of Medicine at Mount SinaiErwin B. Bottinger, Icahn School of Medicine at Mount SinaiJussi Hernesniemi, Fimlab Laboratories and University of Tampere School of MedicineCecilia M. Lindgren, University of OxfordJorje Wong, McMaster UniversityJie Huang, Boston VA Research InstituteMarkku Eskola, University of TampereAndrew P. Morris, University of OxfordIan Ford, University of GlasgowAlex P. Reiner, University of WashingtonGraciela Delgado, Heidelberg UniversityLin Y. Chen, University of MinnesotaYii-Der Ida Chen, Harbor-UCLA Medical CenterRoopinder K. Sandhu, University of AlbertaMan Li, Massachusetts General HospitalEric Boerwinkle, Baylor College of MedicineLewin Eisele, University Duisburg-EssenLars Lannfelt, Uppsala UniversityNatalia Rost, The Broad Institute of MIT and HarvardChristopher D. Anderson, The Broad Institute of MIT and HarvardKent D. Taylor, Harbor-UCLA Medical CenterArchie Campbell, University of EdinburghPatrik K. Magnusson, Karolinska InstitutetDavid Porteous, University of EdinburghLynne J. Hocking, University of AberdeenEfthymia Vlachopoulou, University of HelsinkiNancy L. Pedersen, Karolinska InstitutetKjell Nikus, University of TampereMarju Orho-Melander, Lund UniversityAnders Hamsten, Karolinska InstitutetJan Heeringa, Erasmus University Medical Center RotterdamJoshua C Denny, Vanderbilt UniversityJennifer Kriebel, Helmholtz Zentrum Munchen German Res Ctr EnvironmDawood Darbar, University of IllinoisChristopher Newton-Cheh, The Broad Institute of MIT and HarvardChristian Shaffer, Vanderbilt UniversityPeter W. Macfarlane, University of GlasgowStefanie Heilmann-Heimbach, University of BonnPeter Almgren, Lund UniversityPaul L. Huang, The Broad Institute of MIT and HarvardNona Sotoodehnia, University of WashingtonElsayed Z. Soliman, Wake Forest School of MedicineAndre G. Uitterlinden, Erasmus University Medical Center RotterdamAlbert Hofman, Erasmus University Medical Center RotterdamOscar H. Franco, Erasmus University Medical Center RotterdamUwe Voelker, DZHK (German Centre for Cardiovascular Research)Karl-Heinz Joeckel, University Duisburg-EssenMoritz F. Sinner, University Hospital MunichHenry J. Lin, Harbor-UCLA Medical CenterXiuqing Guo, Harbor-UCLA Medical CenterMartin Dichgans, Klinikum der Universität MünchenErik Ingelsson, Uppsala UniversityCharles Kooperberg, University of WashingtonOlle Melander, Lund UniversityRuth J. F. Loos, Icahn School of Medicine at Mount SinaiJari Laurikka, University of TampereDavid Conen, University Hospital BaselJonathan Rosand, The Broad Institute of MIT and HarvardPim van der Harst, University of GroningenMarja-Liisa Lokki, University of HelsinkiSekar Kathiresan, The Broad Institute of MIT and HarvardAlexandre Pereira, University of Sao PauloJ. Wouter Jukema, Leiden UniversityCaroline Hayward, University of EdinburghJerome I. Rotter, Harbor-UCLA Medical CenterWinfried Maerz, Medical University of GrazTerho Lehtimaki, Fimlab Laboratories and University of Tampere School of MedicineBruno H. Stricker, Erasmus University Medical Center RotterdamMina K. Chung, Cleveland ClinicStephan B. Felix, University Medicine GreifswaldVilmundur Gudnason, Icelandic Heart AssociationAlvaro Alonso, Emory UniversityDan M. Roden, Vanderbilt UniversityStefan Kaeaeb, University Hospital MunichDaniel I. Chasman, The Broad Institute of MIT and HarvardSusan R. Heckbert, University of WashingtonEmelia J. Benjamin, NHLBI and Boston University’s Framingham Heart StudyToshihiro Tanaka, RIKEN Center for Integrative Medical SciencesKathryn L. Lunetta, NHLBI and Boston University’s Framingham Heart StudySteven A. Lubitz, The Broad Institute of MIT and HarvardPatrick T. Ellinor, The Broad Institute of MIT and Harvard

Language

English

Date

2017-06-01

Publisher

Nature Publishing Group

Publication Version

Author Accepted Manuscript (After Peer Review)

Copyright Statement

Final Published Version (URL)

http://dx.doi.org/10.1038/ng.3843

Title of Journal or Parent Work

Nature Genetics

ISSN

1061-4036

Volume

Issue

Start Page

End Page

Supplemental Material (URL)

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 Notes

Corresponding author: Patrick T. Ellinor, MD, PhD, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cardiovascular Research Center, Massachusetts General Hospital; Boston, MA 02129, T: 617-724-8729, ellinor@mgh.harvard.edu

Keywords

Research Categories

Health Sciences, Public Health
Health Sciences, Epidemiology

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

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