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Common variants in KCNN3 are associated with lone atrial fibrillation.

Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
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, BHCh, 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<p>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.</p>
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
N01 HC055022 / HC / NHLBI NIH HHS / United States
M01 RR000069-43 / RR / NCRR NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
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
R21 DA027021 / DA / NIDA NIH HHS / United States
R01HL092217 / HL / NHLBI NIH HHS / United States
N01 AG012100 / AG / NIA NIH HHS / United States
R01 HL092217-01A2 / HL / NHLBI NIH HHS / United States
R01 HL092217 / HL / NHLBI NIH HHS / United States
R01HL092577 / HL / NHLBI NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 HG004402-01 / HG / NHGRI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
R01 HL104156 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL068986 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
M01 RR000069 / RR / NCRR NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
1R21DA027021 / DA / NIDA NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
T32 HL007575 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HL080295-01 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HL087652-01 / HL / NHLBI NIH HHS / United States
UL1 RR025774 / RR / NCRR NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 HL076784 / HL / NHLBI NIH HHS / United States
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
U01 HL065962 / HL / NHLBI NIH HHS / United States
R01 HL086694-01A1 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
R01 HL090620 / HL / NHLBI NIH HHS / United States
RC1HL101056 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
R01 DK033651 / DK / NIDDK NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
RC1 HL101056-01 / RC / CCR NIH HHS / United States
R01 HL068986-05A2 / HL / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R21 DA026982 / DA / NIDA NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
U01 HL065962-01A1 / HL / NHLBI NIH HHS / United States
U10 HL054512-05 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
R01 HL090620-01A1 / HL / NHLBI NIH HHS / United States
P30 DK063491-07 / DK / NIDDK NIH HHS / United States
M01RR00069 / RR / NCRR NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
P50 HL077107-03 / HL / NHLBI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
HL076784 / HL / NHLBI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
UL1 RR025005-01 / RR / NCRR NIH HHS / United States
UL1 RR025774-01 / RR / NCRR NIH HHS / United States
U01HL65962 / HL / NHLBI NIH HHS / United States
R01 HL092577-01A1 / HL / NHLBI NIH HHS / United States
N01-AG-12100 / AG / NIA NIH HHS / United States
P01 HL 076491 / HL / NHLBI NIH HHS / United States
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
N01 HC055020 / HC / NHLBI NIH HHS / United States
U10HL054512 / HL / NHLBI NIH HHS / United States
RC1 HL101056-01 / HL / NHLBI NIH HHS / United States
1R01AG028321 / AG / NIA NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
R01 AG028321 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
UL1 RR024989-03 / RR / NCRR NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
R01 HL076784-01 / HL / NHLBI NIH HHS / United States
P01 HL076491-01 / HL / NHLBI NIH HHS / United States
P50 HL077107 / HL / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
UL1 RR025005-025914 / RR / NCRR NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
U01 HL065962-09 / HL / NHLBI NIH HHS / United States
RR025774 / RR / NCRR NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States

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