Genetic determinants

Summary

Number of Patients

1500

Coordinating Investigator

Prof. Stefan Kääb, Munich, Germany

Overall Responsibility

Atrial Fibrillation NETwork (AFNET), Münster, Germany

Current Status

completed

Funding:

German Federal Ministry of Education and Research

Target

The target of the project was to identify new disease genes for atrial fibrillation and risk gene variants that lead to a predisposition for atrial fibrillation.

 

Results

1500 patients diagnosed with atrial fibrillation before their 60th birthday were identified and included in this atrial fibrillation genetics study called  AFNET 1 registry. The data from blood and DNA samples from these patients were later incorporated into a large genome-wide association study. See CHARGE-AF

 

Publications

Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV, Arking DE, Müller-Nurasyid M, Krijthe BP, Lubitz SA, Bis JC, Chung MK, Dörr M, Ozaki K, Roberts JD, Smith JG, Pfeufer A, Sinner MF, Lohman K, Ding J, Smith NL, Smith JD, Rienstra M, Rice KM, Van Wagoner DR, Magnani JW, Wakili R, Clauss S, Rotter JI, Steinbeck G, Launer LJ, Davies RW, Borkovich M, Harris TB, Lin H, Völker U, Völzke H, Milan DJ, Hofman A, Boerwinkle E, Chen LY, Soliman EZ, Voight BF, Li G, Chakravarti A, Kubo M, Tedrow UB, Rose LM, Ridker PM, Conen D, Tsunoda T, Furukawa T, Sotoodehnia N, Xu S, Kamatani N, Levy D, Nakamura Y, Parvez B, Mahida S, Furie KL, Rosand J, Muhammad R, Psaty BM, Meitinger T, Perz S, Wichmann HE, Witteman JC, Kao WH, Kathiresan S, Roden DM, Uitterlinden AG, Rivadeneira F, McKnight B, Sjögren M, Newman AB, Liu Y, Gollob MH, Melander O, Tanaka T, Stricker BH, Felix SB, Alonso A, Darbar D, Barnard J, Chasman DI, Heckbert SR, Benjamin EJ, Gudnason V, Kääb S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet 2012; 44(6):670-5. doi: 10.1038/ng.2261

Ellinor PT, Lunetta KL, Glazer NL, Pfeufer A, Alonso A, Chung MK, Sinner MF, de Bakker PI, Mueller M, Lubitz SA, Fox E, Darbar D, Smith NL, Smith JD, Schnabel RB, Soliman EZ, Rice KM, Van Wagoner DR, Beckmann BM, van Noord C, Wang K, Ehret GB, Rotter JI, Hazen SL, Steinbeck G, Smith AV, Launer LJ, Harris TB, Makino S, Nelis M, Milan DJ, Perz S, Esko T, Köttgen A, Moebus S, Newton-Cheh C, Li M, Möhlenkamp S, Wang TJ, Kao WH, Vasan RS, Nöthen MM, MacRae CA, Stricker BH, Hofman A, Uitterlinden AG, Levy D, Boerwinkle E, Metspalu A, Topol EJ, Chakravarti A, Gudnason V, Psaty BM, Roden DM, Meitinger T, Wichmann HE, Witteman JC, Barnard J, Arking DE, Benjamin EJ, Heckbert SR, Kääb S. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet. 2010 Mar;42(3):240-4.

Kääb S, Darbar D, van Noord C, Dupuis J, Pfeufer A, Newton-Cheh C, Schnabel R, Makino S, Sinner MF, Kannankeril PJ, Beckmann BM, Choudry S, Donahue BS, Heeringa J, Perz S, Lunetta KL, Larson MG, Levy D, Macrae CA, Ruskin JN, Wacker A, Schömig A, Wichmann HE, Steinbeck G, Meitinger T, Uitterlinden AG, Witteman JC, Roden DM, Benjamin EJ, Ellinor PT. Large scale replication and meta-analysis of variants on chromosome 4q25 ssociated with atrial fibrillation. Eur Heart J. 2009; 30(7):813-9.

Sinner MF, Ellinor PT, Meitinger T, Benjamin EJ, Kääb S. Genome-wide association studies of atrial fibrillation: past, present, and future. Cardiovasc Res. 2011;89:701-9. Review. DOI:10.1093/cvr/cvr001.

Sinner MF, Lubitz SA, Pfeufer A, Makino S, Beckmann BM, Lunetta KL, Steinbeck G, Perz S, Rahman R, Sonni A, Greenberg SM, Furie KL, Wichmann HE, Meitinger T, Peters A, Benjamin EJ, Rosand J, Ellinor PT, Kääb S. Lack of replication in polymorphisms reported to be associated with atrial fibrillation. Heart Rhythm. 2011;8:403-9. DOI:10.1016/j.hrthm.2010.11.003.

Sinner MF, Pfeufer A, Akyol M, Beckmann BM, Hinterseer M, Wacker A, Perz S, Sauter W, Illig T, Näbauer M, Schmitt C, Wichmann HE, Schömig A, Steinbeck G, Meitinger T, Kääb S. 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. 2008; 29:907-14.