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Common variants in KCNN3 are associated with lone atrial fibrillation.

TitleCommon variants in KCNN3 are associated with lone atrial fibrillation.
Publication TypeJournal Article
Year of Publication2010
AuthorsEllinor 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 B-M, 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, Kao LWH, Vasan RS, Nöthen MM, MacRae CA, Stricker B CH, Hofman A, Uitterlinden AG, Levy D, Boerwinkle E, Metspalu A, Topol EJ, Chakravarti A, Gudnason V, Psaty BM, Roden DM, Meitinger T, Wichmann H-E, Witteman JCM, Barnard J, Arking DE, Benjamin EJ, Heckbert SR, Kääb S
JournalNat Genet
Volume42
Issue3
Pagination240-4
Date Published2010 Mar
ISSN1546-1718
KeywordsAdolescent, Adult, Aged, Atrial Fibrillation, Case-Control Studies, Cohort Studies, Female, Genome-Wide Association Study, Humans, Introns, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Small-Conductance Calcium-Activated Potassium Channels, Young Adult
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 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.

DOI10.1038/ng.537
Alternate JournalNat Genet
PubMed ID20173747
PubMed Central IDPMC2871387
Grant ListUL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
R01 AG028321-01 / AG / NIA NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
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M01 RR000069-43 / RR / NCRR NIH HHS / United States
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R01 HL059367-02 / HL / NHLBI NIH HHS / United States
UL1 RR024989 / RR / NCRR NIH HHS / United States
CTSA 1UL-RR024989 / RR / NCRR NIH HHS / United States
R21 DA027021-01 / DA / NIDA NIH HHS / United States
T32 HL007575-25 / HL / NHLBI NIH HHS / United States
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RC1 HL101056-01 / HL / NHLBI NIH HHS / United States
N01 AG012100 / AG / NIA NIH HHS / United States
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UL1 RR025005 / RR / NCRR NIH HHS / United States
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U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
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1R21DA027021 / DA / NIDA NIH HHS / United States
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T32 HL007575 / HL / NHLBI NIH HHS / United States
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HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
RC1 HL101056 / HL / NHLBI NIH HHS / United States
P01 HL076491 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
P30 DK063491-02 / DK / NIDDK NIH HHS / United States
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N01-AG-12100 / AG / NIA NIH HHS / United States
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R01 HL087641-01 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
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N01-HC-55018 / HC / NHLBI NIH HHS / United States
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R01 HL087641 / HL / NHLBI NIH HHS / United States
UL1 RR024989-03 / RR / NCRR NIH HHS / United States
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R01 HL076784-01 / HL / NHLBI NIH HHS / United States
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