Common variants in KCNN3 are associated with lone atrial fibrillation

PT Ellinor, KL Lunetta, NL Glazer, A Pfeufer, A Alonso, MK Chung, MF Sinner, PIW de Bakker, M Mueller, SA Lubitz, E Fox, D Darbar, NL Smith, JD Smith, RB Schnabel, EZ Soliman, KM Rice, DR Van Wagoner, BM Beckmann, Charlotte NoordK Wang, GB Ehret, JI Rotter, SL Hazen, G Steinbeck, AV Smith, LJ (Lenore) Launer, TB Harris, S Makino, M Nelis, DJ Milan, S Perz, T Esko, A Kottgen, S Moebus, C Newton-Cheh, M Li, S Moehlenkamp, TJ Wang, WHL Kao, RS Vasan, MM Nothen, CA MacRae, Bruno Stricker, Bert Hofman, André Uitterlinden, D Levy, E Boerwinkle, A Metspalu, EJ Topol, A Chakravarti, V Gudnason, BM Psaty, DM Roden, T Meitinger, HE Wichmann, JCM Witteman, J Barnard, DE Arking, EJ Benjamin, SR Heckbert, S Kaab

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371 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)240-U36
JournalNature Genetics
Volume42
Issue number3
DOIs
Publication statusPublished - 2010

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