Common variants in KCNN3 are associated with lone atrial fibrillation.

Common variants in KCNN3 are associated with lone atrial fibrillation.

Nature genetics (2010-02-23)

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, Tõnu 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

PMID20173747

摘要

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.