Validation of a genetic risk score for atrial fibrillation: A prospective multicenter cohort study

1. Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133: e38–360. doi: 10.1161/CIR.0000000000000350 26673558

2. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366:120–9. doi: 10.1056/NEJMoa1105575 22236222

3. Wolf PA, Kannel WB, Thomas HE, Dawber TR. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: The Framingham study. Neurology. 1978;28:973–7. 570666

4. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham study. Arch Intern Med. 1987;147:1561–4. 3632164

5. Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112:1142–7. doi: 10.1016/j.amjcard.2013.05.063 23831166

6. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R, et al. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST). Circulation. 2003;107:1614–9. doi: 10.1161/01.CIR.0000057981.70380.45 12668495

7. Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Hilker C, et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol. 2009;2:474–80. doi: 10.1161/CIRCEP.109.849638 19843914

8. Kaasenbrood F, Hollander M, Rutten FH, Gerhards LJ, Hoes AW, Tieleman RG. Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination. Europace. 2016;18:1514–20. doi: 10.1093/europace/euv426 26851813

9. Chan N, Choy C. Screening for atrial fibrillation in 13 122 Hong Kong citizens with smartphone electrocardiogram. Heart. 2017;103:24–31. doi: 10.1136/heartjnl-2016-309993 27733533

10. Lowres N, Neubeck L, Salkeld G, Krass I, McLachlan AJ, Redfern J, et al. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study. Thromb Haemost. 2014;111:1167–76. doi: 10.1160/TH14-03-0231 24687081

11. Svennberg E, Engdahl J, Al-Khalili F, Friberg L, Frykman V, Rosenqvist M. Mass screening for untreated atrial fibrillation: the STROKESTOP study. Circulation. 2015;131:2176–84. doi: 10.1161/CIRCULATIONAHA.114.014343 25910800

12. Hess PL, Healey JS, Granger CB, Connolly SJ, Ziegler PD, Alexander JH, et al. the role of cardiovascular implantable electronic devices in the detection and treatment of subclinical atrial fibrillation. JAMA Cardiol. 2017;;2:324–31. doi: 10.1001/jamacardio.2016.5167 28097334

13. Alonso A, Norby FL. Predicting atrial fibrillation and its complications. Circ J. 2016;80:1061–6. doi: 10.1253/circj.CJ-16-0239 27008924

14. Christophersen IE, Yin X, Larson MG, Lubitz SA, Magnani JW, McManus DD, et al. A comparison of the CHARGE-AF and the CHA2DS2-VASc risk scores for prediction of atrial fibrillation in the Framingham Heart Study. Am Heart J. 2016;178:45–54. doi: 10.1016/j.ahj.2016.05.004 27502851

15. Kolek MJ, Graves AJ, Xu M, Bian A, Teixeira PL, Shoemaker MB, et al. Evaluation of a prediction model for the development of atrial fibrillation in a repository of electronic medical records. JAMA Cardiol. 2016;1:1007–13. doi: 10.1001/jamacardio.2016.3366 27732699

16. Lubitz SA, Yin X, Fontes JD, Magnani JW, Rienstra M, Pai M, et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA. 2010;304:2263–9. doi: 10.1001/jama.2010.1690 21076174

17. Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A, et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature. 2007;448:353–7. doi: 10.1038/nature06007 17603472

18. Lubitz SA, Sinner MF, Lunetta KL, Makino S, Pfeufer A, Rahman R, et al. Independent susceptibility markers for atrial fibrillation on chromosome 4q25. Circulation. 2010;122:976–84. doi: 10.1161/CIRCULATIONAHA.109.886440 20733104

19. Benjamin EJ, Rice KM, Arking DE, Pfeufer A, van Noord C, Smith AV, et al. Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. Nat Genet. 2009;41:879–81. doi: 10.1038/ng.416 19597492

20. Ellinor PT, Lunetta KL, Glazer NL, Pfeufer A, Alonso A, Chung MK, et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet. 2010;42:240–4. doi: 10.1038/ng.537 20173747

21. Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV, et al. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet. 2012;44:670–5. doi: 10.1038/ng.2261 22544366

22. Christophersen IE, 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;49:946–52. doi: 10.1038/ng.3843 28416818

23. Tucker NR, Clauss S, Ellinor PT. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism. Cardiovasc Res. 2016;109:493–501. doi: 10.1093/cvr/cvv283 26733238

24. Goldstein BA, Yang L, Salfati E, Assimes TL. Contemporary considerations for constructing a genetic risk score: an empirical approach. Genet Epidemiol. 2015;39:439–45. doi: 10.1002/gepi.21912 26198599

25. Smith JA, Ware EB, Middha P, Beacher L, Kardia SLR. Current applications of genetic risk scores to cardiovascular outcomes and subclinical phenotypes. Curr Epidemiol Rep. 2015;2:180–90. doi: 10.1007/s40471-015-0046-4 26269782

26. Everett BM, Cook NR, Conen D, Chasman DI, Ridker PM, Albert CM. Novel genetic markers improve measures of atrial fibrillation risk prediction. Eur Heart J. 2013;34:2243–51. doi: 10.1093/eurheartj/eht033 23444395

27. Tada H, Shiffman D, Smith JG, Sjögren M, Lubitz SA, Ellinor PT, et al. Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke. Stroke. 2014;45:2856–62. doi: 10.1161/STROKEAHA.114.006072 25123217

28. Lubitz SA, Lunetta KL, Lin H, Arking DE, Trompet S, Li G, et al. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese. J Am Coll Cardiol. 2014;63:1200–10. doi: 10.1016/j.jacc.2013.12.015 24486271

29. Lubitz SA, Yin X, Lin HJ, Kolek M, Smith JG, Trompet S, et al. Genetic risk prediction of atrial fibrillation. Circulation. 2017;135:1311–20. doi: 10.1161/CIRCULATIONAHA.116.024143 27793994

30. Schnabel RB, Sullivan LM, Levy D, Pencina MJ, Massaro JM, D’Agostino RB, et al. Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study. Lancet. 2009;373:739–45. doi: 10.1016/S0140-6736(09)60443-8 19249635

31. Liao J, Khalid Z, Scallan C, Morillo C, O’Donnell M. Noninvasive cardiac monitoring for detecting paroxysmal atrial fibrillation or flutter after acute ischemic stroke: a systematic review. Stroke. 2007;38:2935–40. doi: 10.1161/STROKEAHA.106.478685 17901394

32. Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. 2015;385:2264–71. doi: 10.1016/S0140-6736(14)61730-X 25748612

33. Barrett PM, Komatireddy R, Haaser S, Topol S, Sheard J, Encinas J, et al. Comparison of 24-hour Holter monitoring with 14-day novel adhesive patch electrocardiographic monitoring. Am J Med. 2014;127:95.e11–7.

34. Sanna T, Diener H-C, Passman RS, Di Lazzaro V, Bernstein R a, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478–86. doi: 10.1056/NEJMoa1313600 24963567

35. Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370:2467–77. doi: 10.1056/NEJMoa1311376 24963566

36. Kishore A, Vail A, Majid A, Dawson J, Lees KR, Tyrrell PJ, et al. Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis. Stroke. 2014;45:520–6. doi: 10.1161/STROKEAHA.113.003433 24385275

37. Arboix A, Alió J. Cardioembolic stroke: clinical features, specific cardiac disorders and prognosis. Curr Cardiol Rev. 2010;6:150–61. doi: 10.2174/157340310791658730 21804774

38. Popejoy AB, Fullerton SM. Genomics is failing on diversity. Nature. 2016;538:161–4. doi: 10.1038/538161a 27734877

39. Marcus GM, Alonso A, Peralta CA, Lettre G, Vittinghoff E, Lubitz SA, et al. European ancestry as a risk factor for atrial fibrillation in African Americans. Circulation. 2010;122:2009–15. doi: 10.1161/CIRCULATIONAHA.110.958306 21098467

40. Manrai AK, Funke BH, Rehm HL, Olesen MS, Maron BA, Szolovits P, et al. Genetic misdiagnoses and the potential for health disparities. N Engl J Med. 2016;375:655–65. doi: 10.1056/NEJMsa1507092 27532831

41. Rosenberg NA, Huang L, Jewett EM, Szpiech ZA, Jankovic I, Boehnke M. Genome-wide association studies in diverse populations. Nat Rev Genet. 2010;11:356–66. doi: 10.1038/nrg2760 20395969

42. Roberts JD, Hu D, Heckbert SR, Alonso A, Dewland TA, Vittinghoff E, et al. Genetic investigation into the differential risk of atrial fibrillation among black and white individuals. JAMA Cardiol. 2016;1:442–50. doi: 10.1001/jamacardio.2016.1185 27438321

43. Sinner MF, Tucker NR, Lunetta KL, Ozaki K, Smith JG, Trompet S, et al. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation. Circulation. 2014;130:1225–35. doi: 10.1161/CIRCULATIONAHA.114.009892 25124494

44. Manolio TA. Bringing genome-wide association findings into clinical use. Nat Rev Genet. 2013;14:549–58. doi: 10.1038/nrg3523 23835440