Common variants in KCNN3 are associated with lone atrial fibrillation

Patrick T. Ellinor; Kathryn L. Lunetta; Nicole L. Glazer; Arne Pfeufer; Alvaro Alonso; Mina K. Chung; Moritz F. Sinner; Paul I.W. De Bakker; Martina Mueller; Steven A. Lubitz; Ervin Fox; Dawood Darbar; Nicholas L. Smith; Jonathan D. Smith; Renate B. Schnabel; Elsayed Z. Soliman; Kenneth M. Rice; David R. Van Wagoner; Britt M. Beckmann; Charlotte Van Noord; Ke Wang; Georg B. Ehret; Jerome I. Rotter; Stanley L. Hazen; Gerhard Steinbeck; Albert V. Smith; Lenore J. Launer; Tamara B. Harris; Seiko Makino; Mari Nelis; David J. Milan; Siegfried Perz; Tnu Esko; Anna Köttgen; Susanne Moebus; Christopher Newton-Cheh; Man Li; Stefan Möhlenkamp; Thomas J. Wang; W. H. Linda Kao; Ramachandran S. Vasan; Markus M. Nöthen; Calum A. MacRae; Bruno H. Ch Stricker; Albert Hofman; André G. Uitterlinden; Daniel Levy; Eric Boerwinkle; Andres Metspalu; Eric J. Topol; Aravinda Chakravarti; Vilmundur Gudnason; Bruce M. Psaty; Dan M. Roden; Thomas Meitinger; H. Erich Wichmann; Jacqueline C.M. Witteman; John Barnard; Dan E. Arking; Emelia J. Benjamin; Susan R. Heckbert; Stefan Kääb

doi:10.1038/ng.537

Common variants in KCNN3 are associated with lone atrial fibrillation

Patrick T. Ellinor
, Kathryn L. Lunetta
, Nicole L. Glazer
, Arne Pfeufer
, Alvaro Alonso
, Mina K. Chung
, Moritz F. Sinner
, Paul I.W. De Bakker
, Martina Mueller
, Steven A. Lubitz
, Ervin Fox
, Dawood Darbar
, Nicholas L. Smith
, Jonathan D. Smith
, Renate B. Schnabel
, Elsayed Z. Soliman
, Kenneth M. Rice
, David R. Van Wagoner
, Britt M. Beckmann
, Charlotte Van Noord

Ke Wang, Georg B. Ehret, Jerome I. Rotter, Stanley L. Hazen, Gerhard Steinbeck, Albert V. Smith, Lenore J. Launer, Tamara B. Harris, Seiko Makino, Mari Nelis, David J. Milan, Siegfried Perz, Tnu Esko, Anna Köttgen, Susanne Moebus, Christopher Newton-Cheh, Man Li, Stefan Möhlenkamp, Thomas J. Wang, W. H. Linda Kao, Ramachandran S. Vasan, Markus M. Nöthen, Calum A. MacRae, Bruno H. Ch Stricker, Albert Hofman, André G. Uitterlinden, Daniel Levy, Eric Boerwinkle, Andres Metspalu, Eric J. Topol, Aravinda Chakravarti, Vilmundur Gudnason, Bruce M. Psaty, Dan M. Roden, Thomas Meitinger, H. Erich Wichmann, Jacqueline C.M. Witteman, John Barnard, Dan E. Arking, Emelia J. Benjamin, Susan R. Heckbert, Stefan Kääb

Medicine and Health

Massachusetts General Hospital
Boston University
Framingham Heart Study
University of Washington School of Medicine
Technical University of Munich
Helmholtz Zentrum München German Research Center for Environmental Health
School of Public Health
Cleveland Clinic Foundation
Ludwig-Maximilians-Universität München
Brigham and Women's Hospital
Massachusetts Institute of Technology
University of Mississippi Medical Center
Vanderbilt School of Medicine
University of Washington
Department of Veterans Affairs
Wake Forest School of Medicine
Erasmus University Medical Center
Dutch Medicines Evaluation Board
Netherlands Consortium on Healthy Aging
Johns Hopkins School of Medicine
Geneva University Hospitals
Cedars-Sinai Medical Center
Icelandic Heart Association
University of Iceland
National Institute on Aging (NIA)
University of Tartu
University of Tartu
Johns Hopkins University
University of Duisburg-Essen
University Hospital of Essen
Boston University School of Medicine
Rheinische Friedrich-Wilhelms-Universität Bonn
Inspectorate for Health Care
National Heart, Lung, and Blood Institute (NHLBI)
University of Texas Health Science Center at Houston
McGovern Medical School
Scripps Research Institute
Group Health Research Institute

Research output: Contribution to journal › Article › peer-review

431 Scopus citations

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10 12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 × 10 21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

Original language	English
Pages (from-to)	240-244
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	3
DOIs	https://doi.org/10.1038/ng.537
State	Published - Mar 2010

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Ellinor, P. T., Lunetta, K. L., Glazer, N. L., Pfeufer, A., Alonso, A., Chung, M. K., Sinner, M. F., De Bakker, P. I. W., Mueller, M., Lubitz, S. A., Fox, E., Darbar, D., Smith, N. L., Smith, J. D., Schnabel, R. B., Soliman, E. Z., Rice, K. M., Van Wagoner, D. R., Beckmann, B. M., ... Kääb, S. (2010). Common variants in KCNN3 are associated with lone atrial fibrillation. Nature Genetics, 42(3), 240-244. https://doi.org/10.1038/ng.537

@article{3987ff5963d0471fa2d42f39d75b2871,

title = "Common variants in KCNN3 are associated with lone atrial fibrillation",

abstract = "Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 {\texttimes} 10 12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95\% CI 1.40-1.64; P = 1.83 {\texttimes} 10 21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.",

author = "Ellinor, \{Patrick T.\} and Lunetta, \{Kathryn L.\} and Glazer, \{Nicole L.\} and Arne Pfeufer and Alvaro Alonso and Chung, \{Mina K.\} and Sinner, \{Moritz F.\} and \{De Bakker\}, \{Paul I.W.\} and Martina Mueller and Lubitz, \{Steven A.\} and Ervin Fox and Dawood Darbar and Smith, \{Nicholas L.\} and Smith, \{Jonathan D.\} and Schnabel, \{Renate B.\} and Soliman, \{Elsayed Z.\} and Rice, \{Kenneth M.\} and \{Van Wagoner\}, \{David R.\} and Beckmann, \{Britt M.\} and \{Van Noord\}, Charlotte and Ke Wang and Ehret, \{Georg B.\} and Rotter, \{Jerome I.\} and Hazen, \{Stanley L.\} and Gerhard Steinbeck and Smith, \{Albert V.\} and Launer, \{Lenore J.\} and Harris, \{Tamara B.\} and Seiko Makino and Mari Nelis and Milan, \{David J.\} and Siegfried Perz and Tnu Esko and Anna K{\"o}ttgen and Susanne Moebus and Christopher Newton-Cheh and Man Li and Stefan M{\"o}hlenkamp and Wang, \{Thomas J.\} and \{Linda Kao\}, \{W. H.\} and Vasan, \{Ramachandran S.\} and N{\"o}then, \{Markus M.\} and MacRae, \{Calum A.\} and \{Ch Stricker\}, \{Bruno H.\} and Albert Hofman and Uitterlinden, \{Andr{\'e} G.\} and Daniel Levy and Eric Boerwinkle and Andres Metspalu and Topol, \{Eric J.\} and Aravinda Chakravarti and Vilmundur Gudnason and Psaty, \{Bruce M.\} and Roden, \{Dan M.\} and Thomas Meitinger and Wichmann, \{H. Erich\} and Witteman, \{Jacqueline C.M.\} and John Barnard and Arking, \{Dan E.\} and Benjamin, \{Emelia J.\} and Heckbert, \{Susan R.\} and Stefan K{\"a}{\"a}b",

year = "2010",

month = mar,

doi = "10.1038/ng.537",

language = "English",

volume = "42",

pages = "240--244",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

Ellinor, PT, Lunetta, KL, Glazer, NL, Pfeufer, A, Alonso, A, Chung, MK, Sinner, MF, De Bakker, PIW, Mueller, M, Lubitz, SA, Fox, E, Darbar, D, Smith, NL, Smith, JD, Schnabel, RB, Soliman, EZ, Rice, KM, Van Wagoner, DR, Beckmann, BM, Van Noord, C, Wang, K, Ehret, GB, Rotter, JI, Hazen, SL, Steinbeck, G, Smith, AV, Launer, LJ, Harris, TB, Makino, S, Nelis, M, Milan, DJ, Perz, S, Esko, T, Köttgen, A, Moebus, S, Newton-Cheh, C, Li, M, Möhlenkamp, S, Wang, TJ, Linda Kao, WH, Vasan, RS, Nöthen, MM, MacRae, CA, Ch Stricker, BH, Hofman, A, Uitterlinden, AG, Levy, D, Boerwinkle, E, Metspalu, A, Topol, EJ, Chakravarti, A, Gudnason, V, Psaty, BM, Roden, DM, Meitinger, T, Wichmann, HE, Witteman, JCM, Barnard, J, Arking, DE, Benjamin, EJ, Heckbert, SR & Kääb, S 2010, 'Common variants in KCNN3 are associated with lone atrial fibrillation', Nature Genetics, vol. 42, no. 3, pp. 240-244. https://doi.org/10.1038/ng.537

TY - JOUR

T1 - Common variants in KCNN3 are associated with lone atrial fibrillation

AU - Ellinor, Patrick T.

AU - Lunetta, Kathryn L.

AU - Glazer, Nicole L.

AU - Pfeufer, Arne

AU - Alonso, Alvaro

AU - Chung, Mina K.

AU - Sinner, Moritz F.

AU - De Bakker, Paul I.W.

AU - Mueller, Martina

AU - Lubitz, Steven A.

AU - Fox, Ervin

AU - Darbar, Dawood

AU - Smith, Nicholas L.

AU - Smith, Jonathan D.

AU - Schnabel, Renate B.

AU - Soliman, Elsayed Z.

AU - Rice, Kenneth M.

AU - Van Wagoner, David R.

AU - Beckmann, Britt M.

AU - Van Noord, Charlotte

AU - Wang, Ke

AU - Ehret, Georg B.

AU - Rotter, Jerome I.

AU - Hazen, Stanley L.

AU - Steinbeck, Gerhard

AU - Smith, Albert V.

AU - Launer, Lenore J.

AU - Harris, Tamara B.

AU - Makino, Seiko

AU - Nelis, Mari

AU - Milan, David J.

AU - Perz, Siegfried

AU - Esko, Tnu

AU - Köttgen, Anna

AU - Moebus, Susanne

AU - Newton-Cheh, Christopher

AU - Li, Man

AU - Möhlenkamp, Stefan

AU - Wang, Thomas J.

AU - Linda Kao, W. H.

AU - Vasan, Ramachandran S.

AU - Nöthen, Markus M.

AU - MacRae, Calum A.

AU - Ch Stricker, Bruno H.

AU - Hofman, Albert

AU - Uitterlinden, André G.

AU - Levy, Daniel

AU - Boerwinkle, Eric

AU - Metspalu, Andres

AU - Topol, Eric J.

AU - Chakravarti, Aravinda

AU - Gudnason, Vilmundur

AU - Psaty, Bruce M.

AU - Roden, Dan M.

AU - Meitinger, Thomas

AU - Wichmann, H. Erich

AU - Witteman, Jacqueline C.M.

AU - Barnard, John

AU - Arking, Dan E.

AU - Benjamin, Emelia J.

AU - Heckbert, Susan R.

AU - Kääb, Stefan

PY - 2010/3

Y1 - 2010/3

N2 - Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10 12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 × 10 21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

AB - Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10 12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 × 10 21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

UR - https://www.scopus.com/pages/publications/77649191092

U2 - 10.1038/ng.537

DO - 10.1038/ng.537

M3 - Article

C2 - 20173747

AN - SCOPUS:77649191092

SN - 1061-4036

VL - 42

SP - 240

EP - 244

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Common variants in KCNN3 are associated with lone atrial fibrillation

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