Common variants in KCNN3 are associated with lone atrial fibrillation

• Published in: Nature genetics Vol. 42; no. 3; pp. 240 - 244
• Main Authors: Ellinor, Patrick T, Lunetta, Kathryn L, Glazer, Nicole L, Pfeufer, Arne, Alonso, Alvaro, Chung, Mina K, Sinner, Moritz F, de Bakker, Paul I W, Mueller, Martina, Lubitz, Steven A, Fox, Ervin, Darbar, Dawood, Smith, Nicholas L, Smith, Jonathan D, Schnabel, Renate B, Soliman, Elsayed Z, Rice, Kenneth M, Van Wagoner, David R, Beckmann, Britt-M, van Noord, Charlotte, Wang, Ke, 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, Perz, Siegfried, Esko, Tõnu, Köttgen, Anna, Moebus, Susanne, Newton-Cheh, Christopher, Li, Man, Möhlenkamp, Stefan, Wang, Thomas J, Linda Kao, W H, Vasan, Ramachandran S, Nöthen, Markus M, MacRae, Calum A, Ch Stricker, Bruno H, Hofman, Albert, 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, Witteman, Jacqueline C M, Barnard, John, Arking, Dan E, Benjamin, Emelia J, Heckbert, Susan R, Kääb, Stefan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2010; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/457/649; 631/208/727/2000; 692/699/75/29/1309; Adolescent; Adult; Aged; Agriculture; Animal Genetics and Genomics; Atrial fibrillation; Atrial Fibrillation - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cardiac dysrhythmias; Cardiology. Vascular system; Cardiovascular disease; Cardiovascular diseases; Case-Control Studies; Chromosomes; Cohort Studies; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic variance; Genetic variation; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genotype & phenotype; Health aspects; Heart; Human Genetics; Humans; Inflation; Introns - genetics; letter; Male; Mass spectrometry; Medical research; Medical sciences; Meta-analysis; Meta-Analysis as Topic; Middle Aged; Polymorphism, Single Nucleotide - physiology; Risk factors; Small-Conductance Calcium-Activated Potassium Channels - genetics; Studies; Young Adult; United States; Variant; Cardiovascular disease; Arrhythmia; Heart disease; Atrial fibrillation; Excitability disorder
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.537

Patrick Ellinor and colleagues report a genome-wide association study identifying variants in KCNN3 associated to lone atrial fibrillation. 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 × 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 × 10 −21 ). rs13376333 is intronic to KCNN3 , which encodes a potassium channel protein involved in atrial repolarization.