Common variants in KCNN3 are associated with lone atrial fibrillation
Open accessAbstract
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 x 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 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
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The AF-GRS comprises 12 SNPs that had been previously shown to be associated with AF at genome-wide significance.
“The AF-GRS comprised 12 SNPs that had been previously shown to be associated with AF at genome-wide significance.”
From Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke (2014) · cites this paper as [22]
The 12 SNPs in the AF-GRS are all the SNPs that have been reported to be associated with AF at a genome-wide significance level (P<5×10−8).
“These are all the SNPs that have been reported to be associated with AF at a genome-wide significance level (P<5×10−8), including 4 SNPs at PITX2 locus.18-23”
From Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke (2014) · cites this paper as [22]
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- Authors
- 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., van Noord, C., Wang, K., Ehret, G. B., Rotter, J. I., Hazen, S. L., Steinbeck, G., Smith, A. V., Launer, L. J., Harris, T. B., Makino, S., Nelis, M., Milan, D. J., Perz, S., Esko, T., Köttgen, A., Moebus, S., Newton-Cheh, C., Li, M., Möhlenkamp, S., Wang, T. J., Linda Kao, W. H., Vasan, R. S., Nöthen, M. M., MacRae, C. A., Ch Stricker, B. H., Hofman, A., Uitterlinden, A. G., Levy, D., Boerwinkle, E., Metspalu, A., Topol, E. J., Chakravarti, A., Gudnason, V., Psaty, B. M., Roden, D. M., Meitinger, T., Wichmann, H.-E., Witteman, J. C. M., Barnard, J., Arking, D. E., Benjamin, E. J., Heckbert, S. R., & Kääb, S.
- Affiliations
- Massachusetts General Hospital (US)
- Boston University (US)
- University of Washington (US)
- TUM Klinikum (DE)
- Cleveland Clinic (US)
- Ludwig-Maximilians-Universität München (DE)
- Brigham and Women's Hospital (US)
- University of Mississippi Medical Center (US)
- Vanderbilt University (US)
- Framingham Heart Study (US)
- Wake Forest University Health Sciences (US)
- Johns Hopkins University (US)
- Cedars-Sinai Medical Center (US)
- University of Iceland (IS)
- National Institutes of Health (US)
- Estonian Biocentre (EE)
- Helmholtz Munich (DE)
- University of Duisburg-Essen (DE)
- West German Heart and Vascular Center Essen (DE)
- University of Bonn (DE)
- Erasmus MC (NL)
- National Heart, Lung, and Blood Institute (US)
- The University of Texas Health Science Center at Houston (US)
- Scripps Research Institute (US)
- Kaiser Permanente Washington Health Research Institute (US)
- Corresponding author
- Ellinor, Patrick T
- Kääb, Stefan
- ORCID
- Ellinor, Patrick T
- Lunetta, Kathryn L
- Glazer, Nicole L
- Chung, Mina K
- Sinner, Moritz F
- Lubitz, Steven A
- Darbar, Dawood
- Smith, Nicholas L
- Smith, Jonathan D
- Schnabel, Renate B
- Soliman, Elsayed Z
- Rice, Kenneth M
- Ehret, Georg B
- Rotter, Jerome I
- Hazen, Stanley L
- Steinbeck, Gerhard
- Smith, Albert V
- Launer, Lenore J
- Harris, Tamara B
- Makino, Seiko
- Nelis, Mari
- Milan, David J
- Esko, Tõnu
- Köttgen, Anna
- Moebus, Susanne
- Li, Man
- Wang, Thomas J
- Vasan, Ramachandran S
- Nöthen, Markus M
- MacRae, Calum A
- Uitterlinden, André G
- Levy, Daniel
- Boerwinkle, Eric
- Metspalu, Andres
- Topol, Eric J
- Chakravarti, Aravinda
- Gudnason, Vilmundur
- Psaty, Bruce M
- Roden, Dan M
- Meitinger, Thomas
- Wichmann, H-Erich
- Barnard, John
- Arking, Dan E
- Benjamin, Emelia J
- Heckbert, Susan R
- Kääb, Stefan
- Venue
- Nature Genetics
- Published
- 2010-02-21
- Volume
- 42
- Issue
- 3
- Pages
- 240-244
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2871387
- OpenAlex
- W2100414478
- Cited by
- 485
- References
- 37
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 20 · 2023: 18 · 2022: 7 · 2021: 24 · 2020: 21 · 2019: 27 · 2018: 24 · 2017: 30 · 2016: 43 · 2015: 47 · 2014: 44 · 2013: 39 · 2012: 41
- FWCI
- 33.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01ag12100-57-0-2, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc55021-47-0-1, n01hc085085-011, n01hc085083-027, n01hc55020-39-0-0, n01hc085080-026, n01hc55016-37-0-0, n01hc055022-024, n01hc085086-022, n01hc55019-35-0-1, n01hc55018-38-0-1, n01hc25195-41-0-1, n01hc55222-0-0-0, n02hl64278-6-0-0, n01hc075150-004, n01hc035129-010, n01hc55015-48-0-1)
- U.S. Public Health Service (HHSN 268200625226C)
- National Institute on Aging (N01-AG12100, N01-AG012100, R01AG028321)
- National Heart, Lung, and Blood Institute (N01-HC-85081, HL-076784, N01-HC55022, N01 HC085086, N01HC-85083, N01 HC055016, N01-HC-55018, U01 HL-65962, N01 HC 55020, N01 HC085079, N01 HC085083, N01‐HC25195, N01 HC 55019, N01HC85082, N01HC‐75150, N01 HC85086, R01 HL-59367, N01 HC085080, R01HL087652, R01HL068986, N01 HC055020, N01 HC035129, N02 HL064278, N01HC85080, N02- HL-64278, R01HL104156, N01 HC055018, N01 HC015103, N01 HC55222, P50HL077107, N01 HC085085, N01-HC-025195, U10HL054512, N01-HC55016, R01HL087641, N01 HC055022, P01HL076491, R01HL059367, N01HC085082, R01HL092217, U01HL080295, R01HL076784, N01 HC055019, N01 HC055222, R01HL090620, N01 HC085081, U01HL065962, T32HL007575, N01‐HC‐55015, N01-HC55021, RC1HL101056, N01 HC075150, N01 HC055021, N01 HC085084, N01 HC055015, N01 HC045133, R01HL092577, R01HL086694, N01-HC85079)
- National Institute on Drug Abuse (R21DA027021, R21DA026982)
- National Human Genome Research Institute (U01HG004402)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, R01DK033651, P30DK063491)
- National Center for Research Resources (UL1RR024989, UL1RR025005, M01 RR00069, CTSA 1UL-RR024989, UL1RR025774, M01RR000069, RR 025774)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- lone atrial fibrillation, KCNN3, chromosome 1q21, atrial repolarization, potassium channels, genetic susceptibility, common genetic variants, atrial arrhythmias
- MeSH terms
- Adolescent, Adult, Aged, Atrial Fibrillation, Female, Humans, Introns, Male, Middle Aged, Meta-Analysis as Topic, Cohort Studies, Case-Control Studies, Polymorphism, Single Nucleotide, Small-Conductance Calcium-Activated Potassium Channels, Genome-Wide Association Study, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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