Genetics of Atrial Fibrillation: State of the Art in 2017

Heart Lung and Circulation

Volumn 26, Issue 9, 2017, Pages 894-901

  Fatkin, Diane ^a,b,c   Santiago, Celine F ^a   Huttner, Inken G ^a,b   Lubitz, Steven A ^d,e   Ellinor, Patrick T ^d,e  

^a VICTOR CHANG CARDIAC RESEARCH INSTITUTE   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c ST VINCENT S HOSPITAL   (Australia)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

Atrial fibrillation; Genetics; Genomic risk score; Ion channels; Transcription factors

Indexed keywords

ION CHANNEL; TRANSCRIPTION FACTOR;

ACTION POTENTIAL; ARRHYTHMOGENESIS; ATRIAL FIBRILLATION; ENVIRONMENTAL FACTOR; FAMILY; GENE EXPRESSION; GENE LOCUS; GENE MAPPING; GENE MUTATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC PREDISPOSITION; GENETIC VARIATION; GENETICS; HUMAN; LIFESTYLE; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; METABOLISM;

ATRIAL FIBRILLATION; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; HUMANS; ION CHANNELS; TRANSCRIPTION FACTORS;

EID: 85020428879     PISSN: 14439506     EISSN: 14442892     Source Type: Journal    
DOI: 10.1016/j.hlc.2017.04.008     Document Type: Review

References (46)

1. Chen, Y.H., Xu, S.J., Bendahhou, S., Wang, X.L., Wang, Y., Xu, W.Y., et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 299 (2003), 251–254.
2. Christophersen, I.E., Ellinor, P.T., Genetics of atrial fibrillation: from families to genomes. J Hum Genet 61 (2016), 61–70.
3. Liang, B., Soka, M., Christensen, A.H., Olesen, M.S., Larsen, A.P., Knop, F.K., et al. Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis. J Mol Cell Cardiol 67 (2014), 69–76.
4. Christensen, A.H., Chatelain, F.C., Huttner, I.G., Olesen, M.S., Soka, M., Feliciangeli, S., et al. The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size. J Mol Cell Cardiol 97 (2016), 24–35.
5. Ellinor, P.T., Petrov-Kondratov, V.I., Zakharova, E., Nam, E.G., MacRae, C.A., Potassium channel gene mutations rarely cause atrial fibrillation. BMC Med Genet, 7, 2006, 70.
6. Mann, S.A., Otway, R., Guo, G., Soka, M., Karlsdotter, L., Trivedi, G., et al. Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk. J Am Coll Cardiol 59 (2012), 1017–1025.
7. Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17 (2015), 405–424.
8. Golbus, J.R., Puckelwartz, M.J., Fahrenbach, J.P., Dellefave-Castillo, L.M., Wolfgeher, D., McNally, E.M., Population-based variation in cardiomyopathy genes. Circ Cardiovasc Genet 5 (2012), 391–399.
9. Christensen, A.H., Benn, M., Tybjaerg-Hansen, A., Haunso, S., Svendsen, J.H., Missense variants in plakophilin-2 in arrhythmogenic right ventricular cardiomyopathy patients: disease-causing or innocent bystanders?. Cardiology 115 (2010), 148–154.
10. Lek, M., Karczewski, K.J., Minikel, E.V., Samocha, K.E., Banks, E., Fennell, T., et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature, 2016, 285–291.
11. Gudbjartsson, D.F., Arnar, D.O., Helgadottir, S., Holm, H., Sigurdsson, A., Jonasdottir, A., et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 448 (2007), 353–357.
12. Ellinor, P.T., Lunetta, K.L., Albert, C.M., Glazer, N.L., Ritchie, M.D., Smith, A.V., et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet 44 (2012), 670–675.
13. Sinner, M.F., Tucker, N.R., Lunetta, K.L., Ozaki, K., Smith, J.G., Trompet, S., et al. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation. Circulation 130 (2014), 1225–1235.
14. Christophersen, I.E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat Genet, 2017, 10.1038/ng.3843.
15. Low, S.K., Takahashi, A., Ebana, Y., Ozaki, K., Christophersen, I.E., Ellinor, P.T., et al. Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nat Genet, 2017, 10.1038/ng.3842.
16. Zhao, J., Yao, H., Li, Z., Wang, L., Liu, G., Wang, D.W., et al. A novel nonsense mutation in LMNA gene identified by exome sequencing in an atrial fibrillation family. Eur J Med Genet 59 (2016), 396–400.
17. Tucker, N.R., Mahida, S., Ye, J., Abraham, E.J., Mina, J.A., Parsons, V.A., et al. Gain-of-function mutations in GATA6 lead to atrial fibrillation. Heart Rhythm 14 (2017), 284–291.
18. Weeke, P., Muhammad, R., Delaney, J.T., Shafer, C., Mosley, J.D., Blair, M., et al. Whole-exome sequencing in familial atrial fibrillation. Eur Heart J 35 (2014), 2477–2483.
19. Lubitz, S.A., Brody, J.A., Bihlmeyer, N.A., Roselli, C., Weng, L.C., Christophersen, I.E., et al. Whole exome sequencing in atrial fibrillation. PLoS Genetics, 12, 2016, e1006284.
20. Otway, R., Vandenberg, J.I., Guo, G., Varghese, A., Castro, M.L., Liu, J., et al. Stretch-sensitive KCNQ1 mutation: a link between genetic and environmental factors in the pathogenesis of atrial fibrillation?. J Am Coll Cardiol 49 (2007), 578–586.
21. Wang, J., Klysik, E., Sood, S., Johnson, R.L., Wehrens, X.H., Martin, J.F., Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proc Natl Acad Sci USA 107 (2010), 9753–9758.
22. Kirchhof, P., Kahr, P.C., Kaese, S., Piccini, I., Vokshi, I., Scheld, H.H., et al. PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibilty and complex changes in gene expression. Circ Cardiovasc Genet 4 (2011), 123–133.
23. Chinchilla, A., Daimi, H., Lozano-Velasco, E., Dominguez, J.N., Caballero, R., Delpon, E., et al. PITX2 insufficiency leads to atrial electrical and structural remodelling linked to arrhythmogenesis. Circ Cardiovasc Genet 4 (2011), 269–279.
24. Tao, Y., Zhang, M., Li, L., Bai, Y., Zhou, Y., Moon, A.M., et al. Pitx2, an atrial fibrillation predisposition gene, directly regulates ion transport and intercalated disc genes. Circ Cardiovasc Genet 7 (2014), 23–32.
25. Gore-Panter, S.R., Hsu, J., Hanna, P., Gillinov, A.M., Pettersson, G., Newton, D.W., et al. Atrial fibrillation associated chromosome 4q25 variants are not associated with PITX2c expression in human left atrial appendages. PLoS One, 9, 2014, e86245.
26. Lubitz, S.A., Lunetta, K.L., Lin, H., Arking, D.E., Trompet, S., Li, G., et al. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese. J Am Coll Cardiol 63 (2014), 1200–1210.
27. Aguirre, L.A., Alonso, M.E., Badia-Careaga, C., Rollan, I., Arias, C., Fernandez-Minan, A., et al. Long-range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP. BMC Biol, 13, 2015, 26.
28. Nadadur, R.D., Broman, M.T., Boukens, B., Mazurek, S.R., Yang, X., van den Boogaard, M., et al. Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. Sci Transl Med, 8, 2016, 354ra115.
29. Ye, J., Tucker, N.R., Weng, L.C., Clauss, S., Lubitz, S.A., Ellinor, P.T., A functional variant associated with atrial fibrillation regulates PITX2c expression through TFAP2a. Am J Hum Genet 99 (2016), 1281–1291.
30. Boldt, L.H., Posch, M.G., Perrot, A., Plotzki, M., Rolf, S., Parwani, A.S., et al. Mutational analysis of the PITX2 and NKX2-5 genes in patients with idiopathic atrial fibrillation. Int J Cardiol 145 (2010), 316–317.
31. Zhou, Y.M., Zheng, P.X., Yang, Y.Q., Ge, Z.M., Kang, W.Q., A novel PITX2c loss-of-function mutation underlies lone atrial fibrillation. Int J Mol Med 32 (2013), 827–834.
32. Wang, J., Zhang, D.F., Sun, Y.M., Yang, Y.Q., A novel PITX2c loss-of-function mutation associated with familial atrial fibrillation. Eur J Med Genet 57 (2014), 25–31.
33. Liu, C., Liu, W., Palle, J., Lu, M.F., Brown, N.A., Martin, J.F., Pitx2c patterns anterior myocardium and aortic arch vessels and is required for local cell movement into atrioventricular cushions. Development, 129, 2002 5081–91.
34. Mommersteeg, M.T., Brown, N.A., Prall, O.W., de Gier-de Vries, C., Harvey, R.P., Moorman, A.F., et al. Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium. Circ Res 101 (2007), 902–909.
35. Zaidi, S., Brueckner, M., Genetics and genomics of congenital heart disease. Circ Res 120 (2017), 923–940.
36. He, A., Gu, F., Hu, Y., Ma, Q., Ye, L.Y., Akiyama, J.A., et al. Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease. Nat Commun, 5, 2014, 4907.
37. Fatkin, D., Seidman, C.E., Seidman, J.G., Genetics and disease of ventricular muscle. Cold Spring Harb Perspect Med, 4, 2014, a021063.
38. Deshmukh, A., Barnard, J., Sun, H., Newton, D., Castel, L., Pettersson, G., et al. Left atrial transcriptional changes associated with atrial fibrillation susceptibility and persistence. Circ Arrhythmia Electrophysiol 8 (2015), 32–41.
39. Luo, X., Yang, B., Nattel, S., MicroRNAs and atrial fibrillation: mechanisms and translational potential. Nat Rev Cardiol 12 (2015), 80–90.
40. Tao, H., Shi, K.H., Yang, J.J., Li, J., Epigenetic mechanisms in atrial fibrillation: new insights and future directions. Trends Cardiovasc Med 26 (2016), 306–318.
41. Ohanian, M., Humphreys, D.T., Anderson, E., Preiss, T., Fatkin, D., A heterozygous variant in the cardiac miR-133 gene, MIR133A2, alters miRNA duplex processing and strand abundance. BMC Genet, 14, 2013, 18.
42. Ackerman, M.J., Priori, S.G., Willems, S., Berul, C., Brugada, R., Calkins, H., et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies. Europace 13 (2011), 1077–1109.
43. Lubitz, S.A., Yin, X., Lin, H., Kolek, M., Smith, J.G., Trompet, S., et al. Genetic risk prediction of atrial fibrillation. Circulation 135 (2017), 1311–1320.
44. Havulinna, A.S., Kettunen, J., Ukkola, O., Osmond, C., Eriksson, J.G., Kesaniemi, Y.A., et al. A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals. Hypertension 61 (2013), 987–994.
45. Natarajan, P., Young, R., Stitziel, N.O., Padmanabhan, S., Baber, U., Mehran, R., et al. Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting. Circulation, 2017 Feb 27. pii: CIRCULATIONAHA. 116.024436.
46. Chatterjee, N.A., Guilianini, F., Geelhoed, B., Lunetta, K.L., Misialek, J.R., Niemeijer, M.N., et al. Genetic obesity and the risk of atrial fibrillation: causal estimates from Mendelian randomization. Circulation 135 (2017), 741–754.