Very early-onset lone atrial fibrillation patients have a high prevalence of rare variants in genes previously associated with atrial fibrillation

Go, 2001, Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study, JAMA, 285, 2370, 10.1001/jama.285.18.2370 Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119–125. Benjamin, 1998, Impact of atrial fibrillation on the risk of death: the Framingham Heart study, Circulation, 98, 946, 10.1161/01.CIR.98.10.946 Psaty, 1997, Incidence of and risk factors for atrial fibrillation in older adults, Circulation, 96, 2455, 10.1161/01.CIR.96.7.2455 Fuster, 2006, J Am Coll Cardiol, 48, 854, 10.1016/j.jacc.2006.07.009 Mahida, 2011, Monogenic atrial fibrillation as pathophysiological paradigms, Cardiovasc Res, 89, 692, 10.1093/cvr/cvq381 Nattel, 2002, New ideas about atrial fibrillation 50 years on, Nature, 415, 219, 10.1038/415219a Moe, 1975, Evidence for reentry as a mechanism of cardiac arrhythmias, Rev Physiol Biochem Pharmacol, 72, 55, 10.1007/BFb0031546 Yang, 2009, Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation, J Hum Genet, 54, 277, 10.1038/jhg.2009.26 Olesen MS, Nielsen MW, Haunsø S, Svendsen JH. Atrial fibrillation: the role of common and rare genetic variants. Eur J Hum Genet. In press. Christophersen, 2009, Familial aggregation of atrial fibrillation: a study in Danish twins, Circ Arrhythm Electrophysiol, 2, 378, 10.1161/CIRCEP.108.786665 Oyen, 2012, Familial aggregation of lone atrial fibrillation in young persons, J Am Coll Cardiol, 60, 917, 10.1016/j.jacc.2012.03.046 Gudbjartsson, 2007, Variants conferring risk of atrial fibrillation on chromosome 4q25, Nature, 448, 353, 10.1038/nature06007 Manolio, 2009, Finding the missing heritability of complex diseases, Nature, 461, 747, 10.1038/nature08494 Mann, 2012, Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk, J Am Coll Cardiol, 59, 1017, 10.1016/j.jacc.2011.11.039 Darbar, 2013, Genetic mechanisms of atrial fibrillation: impact on response to treatment, Nat Rev Cardiol, 10, 317, 10.1038/nrcardio.2013.53 Olesen, 2012, High prevalence of long qt syndrome-associated SCN5A variants in patients with early-onset lone atrial fibrillation, Circ Cardiovasc Genet, 5, 450, 10.1161/CIRCGENETICS.111.962597 NHLBI GO. Exome Sequencing Project (ESP). Exome Variant Server Web site. http://evs.gs.washington.edu/EVS/. Accessed 24-06-2013. Refsgaard, 2012, Mutation analysis of the candidate genes SCN1B-4B, FHL1, and LMNA in patients with arrhythmogenic right ventricular cardiomyopathy, Appl Transl Genom, 1, 44, 10.1016/j.atg.2012.06.001 Giudicessi, 2012, Phylogenetic and physicochemical analyses enhance the classification of rare nonsynonymous single nucleotide variants in type 1 and 2 long-QT syndrome, Circ Cardiovasc Genet, 5, 519, 10.1161/CIRCGENETICS.112.963785 Benjamin, 2009, Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry, Nat Genet, 41, 879, 10.1038/ng.416 Ellinor, 2010, Common variants in KCNN3 are associated with lone atrial fibrillation, Nat Genet, 42, 240, 10.1038/ng.537 Ellinor, 2012, Meta-analysis identifies six new susceptibility loci for atrial fibrillation, Nat Genet, 44, 670, 10.1038/ng.2261 Piton, 2013, XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing, Am J Hum Genet, 93, 368, 10.1016/j.ajhg.2013.06.013 Risgaard B, Jabbari R, Refsgaard L, et al. High prevalence of genetic variants previously associated with Brugada syndrome in new exome data. Clin Genet. In press. Refsgaard, 2012, High prevalence of genetic variants previously associated with LQT syndrome in new exome data, Eur J Hum Genet, 20, 905, 10.1038/ejhg.2012.23 Sikkema-Raddatz, 2013, Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics, Hum Mutat, 34, 1035, 10.1002/humu.22332 Christophersen, 2013, Rare variants in GJA5 are associated with early-onset lone atrial fibrillation, Can J Cardiol, 29, 111, 10.1016/j.cjca.2012.08.002 Shrickel JW, Lübkemeier I, Nickenig G, Lickfett L, Willecke K. Connexin40 dysfunction in connexin40 A96S point mutated mice results in atrial conduction disturbances and perpetuation of atrial fibrillation. 2011; Abstract PO2-95, Heart Rhythm 2011;8:182. Lübkemeier, 2011, The connexin40 A96S mutation causes renin-dependent hypertension, J Am Soc Nephrol, 22, 1031, 10.1681/ASN.2010101047 Lübkemeier, 2013, The connexin40a96s mutation from a patient with atrial fibrillation causes decreased atrial conduction velocities and sustained episodes of induced atrial fibrillation in mice, J Mol Cell Cardiol, 65, 19, 10.1016/j.yjmcc.2013.09.008 Kitamura, 1999, Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism, Development, 126, 5749, 10.1242/dev.126.24.5749 Nielsen, 2013, J-shaped association between QTc interval duration and the risk of atrial fibrillation: results from the Copenhagen ECG study, J Am Coll Cardiol, 61, 2557, 10.1016/j.jacc.2013.03.032