on June 2, 2003
Circulation. 2003
Published online before print June 2, 2003, doi: 10.1161/01.CIR.0000077910.80718.49
Published online before print June 2, 2003, doi: 10.1161/01.CIR.0000077910.80718.49
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 25, 2003
From the Cardiovascular Research Center, Cardiac Arrhythmia Service, and Cardiology Division, Massachusetts General Hospital, Boston, Mass. * To whom correspondence should be addressed. E-mail: cmacrae{at}partners.org.
Background--Atrial fibrillation (AF), the most common clinical arrhythmia, is a major cause of morbidity and mortality. Although AF is often associated with other cardiovascular conditions, many patients present without an obvious etiology. Inherited forms of AF exist, but the causative gene has been defined only in a single family. We have identified a large family (family FAF-1) in which AF segregates as a Mendelian trait. Methods and Results--Thirty-four family members were evaluated by 12-lead ECG, echocardiogram, 24-hour Holter monitoring, and laboratory studies. Individuals with electrocardiographically documented AF were defined as affected. Subjects were considered unaffected if they were >60 years of age, had no personal history of AF, and had no offspring with a history of AF. DNA was extracted and genotypic analyses were performed using polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 6, with a peak 2-point logarithm of the odds (LOD) score of 3.63 ( Conclusion--We have mapped a novel locus for AF to chromosome 6q14-16. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of AF.
Revised on May 5, 2003
Accepted on May 5, 2003
Locus for Atrial Fibrillation Maps to Chromosome 6q14-16
Patrick T. Ellinor MD, PhD,
=0) at the marker D6S1021. A maximal multipoint LOD score of 4.9 was obtained between D6S286 and D6S1021, indicating odds of 
100 000:1 in favor of this interval as the location of the gene defect responsible for AF in this family. The LOD scores were robust to changes in penetrance and allele frequency. Haplotype analyses further supported this minimal genetic interval.
Key words: arrhythmia • genetics • cardiomyopathy
This article has been cited by other articles:
 |
|
 |
|
  C.-T. Tsai, L.-P. Lai, J.-J. Hwang, J.-L. Lin, and F.-T. Chiang Molecular Genetics of Atrial Fibrillation J. Am. Coll. Cardiol., July 22, 2008; 52(4): 241 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Schoonderwoerd, M. D. Smit, L. Pen, and I. C. Van Gelder New risk factors for atrial fibrillation: causes of 'not-so-lone atrial fibrillation' Europace, June 1, 2008; 10(6): 668 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Darbar, P. J. Kannankeril, B. S. Donahue, G. Kucera, T. Stubblefield, J. L. Haines, A. L. George Jr, and D. M. Roden Cardiac Sodium Channel (SCN5A) Variants Associated with Atrial Fibrillation Circulation, April 15, 2008; 117(15): 1927 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Sinner, A. Pfeufer, M. Akyol, B.-M. Beckmann, M. Hinterseer, A. Wacker, S. Perz, W. Sauter, T. Illig, M. Nabauer, et al. The non-synonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of KCNH2 (HERG) Eur. Heart J., April 1, 2008; 29(7): 907 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Darbar, A. Hardy, J. L. Haines, and D. M. Roden Prolonged signal-averaged P-wave duration as an intermediate phenotype for familial atrial fibrillation. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1083 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. London An irregularly irregular inheritance. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1090 - 1091. [Full Text] [PDF]
|
|
|
|
|
|
D. Fatkin, R. Otway, and J. I. Vandenberg Genes and Atrial Fibrillation: A New Look at an Old Problem Circulation, August 14, 2007; 116(7): 782 - 792. [Full Text] [PDF]
|
|
|
|
|
|
Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): 854 - 906. [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): 700 - 752. [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Eur. Heart J., August 2, 2006; 27(16): 1979 - 2030. [Full Text] [PDF]
|
|
|
|
|
|
C. Fatini, E. Sticchi, M. Genuardi, F. Sofi, F. Gensini, A. M. Gori, M. Lenti, A. Michelucci, R. Abbate, and G. F. Gensini Analysis of minK and eNOS genes as candidate loci for predisposition to non-valvular atrial fibrillation Eur. Heart J., July 2, 2006; 27(14): 1712 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Gollob, D. L. Jones, A. D. Krahn, L. Danis, X.-Q. Gong, Q. Shao, X. Liu, J. P. Veinot, A. S.L. Tang, A. F.R. Stewart, et al. Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N. Engl. J. Med., June 22, 2006; 354(25): 2677 - 2688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. O. Arnar, S. Thorvaldsson, T. A. Manolio, G. Thorgeirsson, K. Kristjansson, H. Hakonarson, and K. Stefansson Familial aggregation of atrial fibrillation in Iceland Eur. Heart J., March 2, 2006; 27(6): 708 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shah, F. G. Akar, and G. F. Tomaselli Molecular Basis of Arrhythmias Circulation, October 18, 2005; 112(16): 2517 - 2529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C.P. Wiesfeld, M. E.W. Hemels, J. P. Van Tintelen, M. P. Van den Berg, D. J. Van Veldhuisen, and I. C. Van Gelder Genetic aspects of atrial fibrillation Cardiovasc Res, August 15, 2005; 67(3): 414 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Temple, P. Frias, J. Rottman, T. Yang, Y. Wu, E. E. Verheijck, W. Zhang, C. Siprachanh, H. Kanki, J. B. Atkinson, et al. Atrial Fibrillation in KCNE1-Null Mice Circ. Res., July 8, 2005; 97(1): 62 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Gersh, T. S.M. Tsang, M. E. Barnes, and J. B. Seward The changing epidemiology of non-valvular atrial fibrillation: the role of novel risk factors Eur. Heart J. Suppl., May 1, 2005; 7(suppl_C): C5 - C11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Oberti, L. Wang, L. Li, J. Dong, S. Rao, W. Du, and Q. Wang Genome-Wide Linkage Scan Identifies a Novel Genetic Locus on Chromosome 5p13 for Neonatal Atrial Fibrillation Associated With Sudden Death and Variable Cardiomyopathy Circulation, December 21, 2004; 110(25): 3753 - 3759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Fox, S. K. Shernan, and S. C. Body Predictive Genomics of Adverse Events After Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2004; 8(4): 297 - 315. [Abstract] [PDF]
|
|
|
|
 |
|
 P T Ellinor, R K Moore, K K Patton, J N Ruskin, M R Pollak, and C A MacRae Mutations in the long QT gene, KCNQ1, are an uncommon cause of atrial fibrillation Heart, December 1, 2004; 90(12): 1487 - 1488. [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Fox, H. Parise, R. B. D'Agostino Sr, D. M. Lloyd-Jones, R. S. Vasan, T. J. Wang, D. Levy, P. A. Wolf, and E. J. Benjamin Parental Atrial Fibrillation as a Risk Factor for Atrial Fibrillation in Offspring JAMA, June 16, 2004; 291(23): 2851 - 2855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Delisle, B. D. Anson, S. Rajamani, and C. T. January Biology of Cardiac Arrhythmias: Ion Channel Protein Trafficking Circ. Res., June 11, 2004; 94(11): 1418 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-T. Tsai, L.-P. Lai, J.-L. Lin, F.-T. Chiang, J.-J. Hwang, M. D. Ritchie, J. H. Moore, K.-L. Hsu, C.-D. Tseng, C.-S. Liau, et al. Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation Circulation, April 6, 2004; 109(13): 1640 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Havranek and F. A. Masoudi What we're talking about when we talk about race J. Am. Coll. Cardiol., February 4, 2004; 43(3): 436 - 437. [Full Text] [PDF]
|
|