Common genetic variation modulating cardiac ECG parameters and susceptibility to sudden cardiac death

Journal of Molecular and Cellular Cardiology

Volumn 52, Issue 3, 2012, Pages 620-629

  Kolder, Iris C R M ^a   Tanck, Michael W T ^a   Bezzina, Connie R ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

ECG; Genome wide association study; Ion channel; Polymorphism; Sudden cardiac death; Ventricular fibrillation

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); COXSACKIE VIRUS AND ADENOVIRUS RECEPTOR; NEURONAL NITRIC OXIDE SYNTHASE; POTASSIUM CHANNEL KCNE1; POTASSIUM CHANNEL KCNQ1; SODIUM CHANNEL NAV1.5; SODIUM CHANNEL NAV1.8;

CHROMOSOME MAP; CORONARY ARTERY DISEASE; CXADR GENE; ELECTROCARDIOGRAPHY; GENE; GENE LOCUS; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC VARIABILITY; HEART CONDUCTION; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEART RATE; HEART REPOLARIZATION; HUMAN; LONG QT SYNDROME; MOLECULAR MECHANICS; NONHUMAN; NOS1AP GENE; PHENOTYPE; PR INTERVAL; PRIORITY JOURNAL; QRS COMPLEX; QT INTERVAL; REVIEW; SHORT QT SYNDROME; SINGLE NUCLEOTIDE POLYMORPHISM; SUDDEN DEATH;

ALLELES; ANIMALS; DEATH, SUDDEN, CARDIAC; ELECTROCARDIOGRAPHY; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HEART RATE; HUMANS; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS;

EID: 84857633679     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2011.12.014     Document Type: Review

References (109)

1. Manolio T.A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A., Hunter D.J., et al. Finding the missing heritability of complex diseases. Nature 2009, 461:747-753.
2. Myerburg R.J., Castellanos A. Cardiac arrest and sudden cardiac death. Braunwald's heart disease: a textbook of cardiovascular medicine 2007, 933-974. Elsevier, Oxford, UK. P. Libby, R.O. Bonow, D.L. Mann, D.P. Zipes (Eds.).
3. Huikuri H.V., Castellanos A., Myerburg R.J. Sudden death due to cardiac arrhythmias. N Engl J Med 2001, 345:1473-1482.
4. Arking D.E., Chugh S.S., Chakravarti A., Spooner P.M. Genomics in sudden cardiac death. Circ Res 2004, 94:712-723.
5. van der Werf C., van Langen I.M., Wilde A.A. Sudden death in the young: what do we know about it and how to prevent?. Circ Arrhythm Electrophysiol 2010, 3:96-104.
6. Watkins H., Ashrafian H., Redwood C. Inherited cardiomyopathies. N Engl J Med 2011, 364:1643-1656.
7. Wilde A.A., Bezzina C.R. Genetics of cardiac arrhythmias. Heart 2005, 91:1352-1358.
8. Zipes D.P., Wellens H.J. Sudden cardiac death. Circulation 1998, 98:2334-2351.
9. Friedlander Y., Siscovick D.S., Weinmann S., Austin M.A., Psaty B.M., Lemaitre R.N., et al. Family history as a risk factor for primary cardiac arrest. Circulation 1998, 97:155-160.
10. Friedlander Y., Siscovick D.S., Arbogast P., Psaty B.M., Weinmann S., Lemaitre R.N., et al. Sudden death and myocardial infarction in first degree relatives as predictors of primary cardiac arrest. Atherosclerosis 2002, 162:211-216.
11. Jouven X., Desnos M., Guerot C., Ducimetiere P. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999, 99:1978-1983.
12. Dekker L.R., Bezzina C.R., Henriques J.P., Tanck M.W., Koch K.T., Alings M.W., et al. Familial sudden death is an important risk factor for primary ventricular fibrillation: a case-control study in acute myocardial infarction patients. Circulation 2006, 114:1140-1145.
13. Kaikkonen K.S., Kortelainen M.L., Linna E., Huikuri H.V. Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event. Circulation 2006, 114:1462-1467.
14. Bezzina C.R., Pazoki R., Bardai A., Marsman R.F., de Jong J.S., Blom M.T., et al. Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction. Nat Genet 2010, 42:688-691.
15. Arking D.E., Reinier K., Post W., Jui J., Hilton G., O'Connor A., et al. Genome-wide association study identifies GPC5 as a novel genetic locus protective against sudden cardiac arrest. PLoS One 2010, 5:e9879.
16. Arking D.E., Junttila M.J., Goyette P., Huertas-Vazquez A., Eijgelsheim M., Blom M.T., et al. Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals. PLoS Genet 2011, 7:e1002158.
17. Asimit J., Zeggini E. Rare variant association analysis methods for complex traits. Annu Rev Genet 2010, 44:293-308.
18. Pe'er I., Yelensky R., Altshuler D., Daly M.J. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 2008, 32:381-385.
19. Bugert P., Elmas E., Stach K., Weiss C., Kalsch T., Dobrev D., et al. No evidence for an association between the rs2824292 variant at chromosome 21q21 and ventricular fibrillation during acute myocardial infarction in a German population. Clin Chem Lab Med 2011, 49:1237-1239.
20. Blow M.J., McCulley D.J., Li Z., Zhang T., Akiyama J.A., Holt A., et al. ChIP-Seq identification of weakly conserved heart enhancers. Nat Genet 2010, 42:806-810.
21. Janse M.J., Kleber A.G. Electrophysiological changes and ventricular arrhythmias in the early phase of regional myocardial ischemia. Circ Res 1981, 49:1069-1081.
22. Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010, 466:707-713.
23. Roden D.M. Drug-induced prolongation of the QT interval. N Engl J Med 2004, 350:1013-1022.
24. Priori S.G., Schwartz P.J., Napolitano C., Bloise R., Ronchetti E., Grillo M., et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003, 348:1866-1874.
25. Chugh S.S. Early identification of risk factors for sudden cardiac death. Nat Rev Cardiol 2010, 7:318-326.
26. Algra A., Tijssen J.G., Roelandt J.R., Pool J., Lubsen J. QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. Circulation 1991, 83:1888-1894.
27. Straus S.M., Kors J.A., De Bruin M.L., van der Hooft C.S., Hofman A., Heeringa J., et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol 2006, 47:362-367.
28. Schwartz P.J., Wolf S. QT interval prolongation as predictor of sudden death in patients with myocardial infarction. Circulation 1978, 57:1074-1077.
29. Chugh S.S., Reinier K., Singh T., Uy-Evanado A., Socoteanu C., Peters D., et al. Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: the Oregon Sudden Unexpected Death Study. Circulation 2009, 119:663-670.
30. Iuliano S., Fisher S.G., Karasik P.E., Fletcher R.D., Singh S.N. QRS duration and mortality in patients with congestive heart failure. Am Heart J 2002, 143:1085-1091.
31. Kashani A., Barold S.S. Significance of QRS complex duration in patients with heart failure. J Am Coll Cardiol 2005, 46:2183-2192.
32. Shamim W., Francis D.P., Yousufuddin M., Varney S., Pieopli M.F., Anker S.D., et al. Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol 1999, 70:171-178.
33. Zimetbaum P.J., Buxton A.E., Batsford W., Fisher J.D., Hafley G.E., Lee K.L., et al. Electrocardiographic predictors of arrhythmic death and total mortality in the multicenter unsustained tachycardia trial. Circulation 2004, 110:766-769.
34. Elhendy A., Hammill S.C., Mahoney D.W., Pellikka P.A. Relation of QRS duration on the surface 12-lead electrocardiogram with mortality in patients with known or suspected coronary artery disease. Am J Cardiol 2005, 96:1082-1088.
35. Horwich T., Lee S.J., Saxon L. Usefulness of QRS prolongation in predicting risk of inducible monomorphic ventricular tachycardia in patients referred for electrophysiologic studies. Am J Cardiol 2003, 92:804-809.
36. Cheng S., Keyes M.J., Larson M.G., McCabe E.L., Newton-Cheh C., Levy D., et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 2009, 301:2571-2577.
37. Soliman E.Z., Prineas R.J., Case L.D., Zhang Z.M., Goff D.C. Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2009, 40:1204-1211.
38. Lemmert M.E., de Jong J.S., van Stipdonk A.M., Crijns H.J., Wellens H.J., Krucoff M.W., et al. Electrocardiographic factors playing a role in ischemic ventricular fibrillation in ST elevation myocardial infarction are related to the culprit artery. Heart Rhythm 2008, 5:71-78.
39. Dyer A.R., Persky V., Stamler J., Paul O., Shekelle R.B., Berkson D.M., et al. Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies. Am J Epidemiol 1980, 112:736-749.
40. Jouven X., Zureik M., Desnos M., Guerot C., Ducimetiere P. Resting heart rate as a predictive risk factor for sudden death in middle-aged men. Cardiovasc Res 2001, 50:373-378.
41. Kannel W.B., Kannel C., Paffenbarger R.S., Cupples L.A. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987, 113:1489-1494.
42. Shaper A.G., Wannamethee G., MacFarlane P.W., Walker M. Heart rate, ischaemic heart disease, and sudden cardiac death in middle-aged British men. Br Heart J 1993, 70:49-55.
43. Arking D.E., Pfeufer A., Post W., Kao W.H., Newton-Cheh C., Ikeda M., et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet 2006, 38:644-651.
44. Chambers J.C., Zhao J., Terracciano C.M., Bezzina C.R., Zhang W., Kaba R., et al. Genetic variation in SCN10A influences cardiac conduction. Nat Genet 2010, 42:149-152.
45. Cho Y.S., Go M.J., Kim Y.J., Heo J.Y., Oh J.H., Ban H.J., et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009, 41:527-534.
46. Eijgelsheim M., Newton-Cheh C., Sotoodehnia N., de Bakker P.I., Muller M., Morrison A.C., et al. Genome-wide association analysis identifies multiple loci related to resting heart rate. Hum Mol Genet 2010, 19:3885-3894.
47. Holm H., Gudbjartsson D.F., Arnar D.O., Thorleifsson G., Thorgeirsson G., Stefansdottir H., et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet 2010, 42:117-122.
48. Newton-Cheh C., Eijgelsheim M., Rice K.M., de Bakker P.I., Yin X., Estrada K., et al. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat Genet 2009, 41:399-406.
49. Nolte I.M., Wallace C., Newhouse S.J., Waggott D., Fu J., Soranzo N., et al. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. PLoS One 2009, 4:e6138.
50. Pfeufer A., Sanna S., Arking D.E., Muller M., Gateva V., Fuchsberger C., et al. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet 2009, 41:407-414.
51. Pfeufer A., van N.C., Marciante K.D., Arking D.E., Larson M.G., Smith A.V., et al. Genome-wide association study of PR interval. Nat Genet 2010, 42:153-159.
52. Smith J.G., Magnani J.W., Palmer C., Meng Y.A., Soliman E.Z., Musani S.K., et al. Genome-wide association studies of the PR interval in African Americans. PLoS Genet 2011, 7:e1001304.
53. Sotoodehnia N., Isaacs A., de Bakker P.I., Dorr M., Newton-Cheh C., Nolte I.M., et al. Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nat Genet 2010, 42:1068-1076.
54. Marroni F., Pfeufer A., Aulchenko Y.S., Franklin C.S., Isaacs A., Pichler I., et al. A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project. Circ Cardiovasc Genet 2009, 2:322-328.
55. Campbell M.C., Tishkoff S.A. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 2008, 9:403-433.
56. Bezzina C.R., Verkerk A.O., Busjahn A., Jeron A., Erdmann J., Koopmann T.T., et al. A common polymorphism in KCNH2 (HERG) hastens cardiac repolarization. Cardiovasc Res 2003, 59:27-36.
57. Gouas L., Nicaud V., Berthet M., Forhan A., Tiret L., Balkau B., et al. Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population. Eur J Hum Genet 2005, 13:1213-1222.
58. Pfeufer A., Jalilzadeh S., Perz S., Mueller J.C., Hinterseer M., Illig T., et al. Common variants in myocardial ion channel genes modify the QT interval in the general population: results from the KORA study. Circ Res 2005, 96:693-701.
59. Lingrel J.B. The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na, K-ATPase. Annu Rev Physiol 2010, 72:395-412.
60. Periasamy M., Bhupathy P., Babu G.J. Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology. Cardiovasc Res 2008, 77:265-273.
61. Milan D.J., Kim A.M., Winterfield J.R., Jones I.L., Pfeufer A., Sanna S., et al. Drug-sensitized zebrafish screen identifies multiple genes, including GINS3, as regulators of myocardial repolarization. Circulation 2009, 120:553-559.
62. Qu X., Jia H., Garrity D.M., Tompkins K., Batts L., Appel B., et al. Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. Dev Biol 2008, 317:486-496.
63. Laitinen P., Fodstad H., Piippo K., Swan H., Toivonen L., Viitasalo M., et al. Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects. Hum Mutat 2000, 15:580-581.
64. Pietila E., Fodstad H., Niskasaari E., Laitinen P.P., Swan H., Savolainen M., et al. Association between HERG K897T polymorphism and QT interval in middle-aged Finnish women. J Am Coll Cardiol 2002, 40:511-514.
65. Newton-Cheh C., Guo C.Y., Larson M.G., Musone S.L., Surti A., Camargo A.L., et al. Common genetic variation in KCNH2 is associated with QT interval duration: the Framingham Heart Study. Circulation 2007, 116:1128-1136.
66. Marjamaa A., Newton-Cheh C., Porthan K., Reunanen A., Lahermo P., Vaananen H., et al. Common candidate gene variants are associated with QT interval duration in the general population. J Intern Med 2009, 265:448-458.
67. Scherer C.R., Lerche C., Decher N., Dennis A.T., Maier P., Ficker E., et al. The antihistamine fexofenadine does not affect I(Kr) currents in a case report of drug-induced cardiac arrhythmia. Br J Pharmacol 2002, 137:892-900.
68. Paavonen K.J., Chapman H., Laitinen P.J., Fodstad H., Piippo K., Swan H., et al. Functional characterization of the common amino acid 897 polymorphism of the cardiac potassium channel KCNH2 (HERG). Cardiovasc Res 2003, 59:603-611.
69. Anson B.D., Ackerman M.J., Tester D.J., Will M.L., Delisle B.P., Anderson C.L., et al. Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels. Am J Physiol Heart Circ Physiol 2004, 286:H2434-H2441.
70. Mannikko R., Overend G., Perrey C., Gavaghan C.L., Valentin J.P., Morten J., et al. Pharmacological and electrophysiological characterization of nine, single nucleotide polymorphisms of the hERG-encoded potassium channel. Br J Pharmacol 2010, 159:102-114.
71. Nishio Y., Makiyama T., Itoh H., Sakaguchi T., Ohno S., Gong Y.Z., et al. D85N, a KCNE1 polymorphism, is a disease-causing gene variant in long QT syndrome. J Am Coll Cardiol 2009, 54:812-819.
72. Paulussen A.D., Gilissen R.A., Armstrong M., Doevendans P.A., Verhasselt P., Smeets H.J., et al. Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients. J Mol Med (Berl) 2004, 82:182-188.
73. Kaab S, Crawford DC, Sinner MF, Behr ER, Kannankeril PJ, Wilde AA et al. A Large Candidate Gene Survey Identifies the KCNE1 D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes. Circ Cardiovasc Genet 2011. [Ahead of print].
74. Nof E., Barajas-Martinez H., Eldar M., Urrutia J., Caceres G., Rosenfeld G., et al. LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current. Europace 2011, 13:1478-1483.
75. Westenskow P., Splawski I., Timothy K.W., Keating M.T., Sanguinetti M.C. Compound mutations: a common cause of severe long-QT syndrome. Circulation 2004, 109:1834-1841.
76. Schott J.J., Alshinawi C., Kyndt F., Probst V., Hoorntje T.M., Hulsbeek M., et al. Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 1999, 23:20-21.
77. Remme C.A., Bezzina C.R. Sodium channel (dys)function and cardiac arrhythmias. Cardiovasc Ther 2010, 28:287-294.
78. Rush A.M., Cummins T.R., Waxman S.G. Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol 2007, 579:1-14.
79. Pallante B.A., Giovannone S., Fang-Yu L., Zhang J., Liu N., Kang G., et al. Contactin-2 expression in the cardiac Purkinje fiber network. Circ Arrhythm Electrophysiol 2010, 3:186-194.
80. Akopian A.N., Souslova V., England S., Okuse K., Ogata N., Ure J., et al. The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 1999, 2:541-548.
81. Postma A.V., Christoffels V.M., Bezzina C.R. Developmental aspects of cardiac arrhythmogenesis. Cardiovasc Res 2011, 91:243-251.
82. Stankunas K., Shang C., Twu K.Y., Kao S.C., Jenkins N.A., Copeland N.G., et al. Pbx/Meis deficiencies demonstrate multigenetic origins of congenital heart disease. Circ Res 2008, 103:702-709.
83. Holm H., Gudbjartsson D.F., Sulem P., Masson G., Helgadottir H.T., Zanon C., et al. A rare variant in MYH6 is associated with high risk of sick sinus syndrome. Nat Genet 2011, 43:316-320.
84. Callis T.E., Pandya K., Seok H.Y., Tang R.H., Tatsuguchi M., Huang Z.P., et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 2009, 119:2772-2786.
85. Scicluna B.P., Wilde A.A., Bezzina C.R. The primary arrhythmia syndromes: same mutation, different manifestations. Are we starting to understand why?. J Cardiovasc Electrophysiol 2008, 19:445-452.
86. Bezzina C., Veldkamp M.W., van den Berg M.P., Postma A.V., Rook M.B., Viersma J.W., et al. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999, 85:1206-1213.
87. Brink P.A., Crotti L., Corfield V., Goosen A., Durrheim G., Hedley P., et al. Phenotypic variability and unusual clinical severity of congenital long-QT syndrome in a founder population. Circulation 2005, 112:2602-2610.
88. Crotti L., Monti M.C., Insolia R., Peljto A., Goosen A., Brink P.A., et al. NOS1AP is a genetic modifier of the long-QT syndrome. Circulation 2009, 120:1657-1663.
89. Tomas M., Napolitano C., De G.L., Bloise R., Subirana I., Malovini A., et al. Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QT syndrome. J Am Coll Cardiol 2010, 55:2745-2752.
90. Chang K.C., Barth A.S., Sasano T., Kizana E., Kashiwakura Y., Zhang Y., et al. CAPON modulates cardiac repolarization via neuronal nitric oxide synthase signaling in the heart. Proc Natl Acad Sci USA 2008, 105:4477-4482.
91. Arking D.E., Chakravarti A. Understanding cardiovascular disease through the lens of genome-wide association studies. Trends Genet 2009, 25:387-394.
92. Freedman M.L., Monteiro A.N., Gayther S.A., Coetzee G.A., Risch A., Plass C., et al. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet 2011, 43:513-518.
93. May D., Blow M.J., Kaplan T., McCulley D.J., Jensen B.C., Akiyama J.A., et al. Large-scale discovery of enhancers from human heart tissue. Nat Genet 2011, 44:89-93.
94. Serre D., Gurd S., Ge B., Sladek R., Sinnett D., Harmsen E., et al. Differential allelic expression in the human genome: a robust approach to identify genetic and epigenetic cis-acting mechanisms regulating gene expression. PLoS Genet 2008, 4:e1000006.
95. Noseworthy P.A., Havulinna A.S., Porthan K., Lahtinen A.M., Jula A., Karhunen P.J., et al. Common genetic variants, QT interval, and sudden cardiac death in a Finnish population-based study. Circ Cardiovasc Genet 2011, 4:305-311.
96. Albert C.M., Nam E.G., Rimm E.B., Jin H.W., Hajjar R.J., Hunter D.J., et al. Cardiac sodium channel gene variants and sudden cardiac death in women. Circulation 2008, 117:16-23.
97. Smith J.G., Lowe J.K., Kovvali S., Maller J.B., Salit J., Daly M.J., et al. Genome-wide association study of electrocardiographic conduction measures in an isolated founder population: Kosrae. Heart Rhythm 2009, 6:634-641.
98. Post W., Shen H., Damcott C., Arking D.E., Kao W.H., Sack P.A., et al. Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish. Hum Hered 2007, 64:214-219.
99. Melton P.E., Haack K., Goring H.H., Laston S., Umans J.G., Lee E.T., et al. Genetic influences on serum bilirubin in American Indians: the Strong Heart Family Study. Am J Hum Biol 2011, 23:118-125.
100. Li J., Huo Y., Zhang Y., Fang Z., Yang J., Zang T., et al. Familial aggregation and heritability of electrocardiographic intervals and heart rate in a rural Chinese population. Ann Noninvasive Electrocardiol 2009, 14:147-152.
101. Im S.W., Lee M.K., Lee H.J., Oh S.I., Kim H.L., Sung J., et al. Analysis of genetic and non-genetic factors that affect the QTc interval in a Mongolian population: the GENDISCAN study. Exp Mol Med 2009, 41:841-848.
102. Newton-Cheh C., Larson M.G., Corey D.C., Benjamin E.J., Herbert A.G., Levy D., et al. QT interval is a heritable quantitative trait with evidence of linkage to chromosome 3 in a genome-wide linkage analysis: the Framingham Heart Study. Heart Rhythm 2005, 2:277-284.
103. Hong Y., Rautaharju P.M., Hopkins P.N., Arnett D.K., Djousse L., Pankow J.S., et al. Familial aggregation of QT-interval variability in a general population: results from the NHLBI Family Heart Study. Clin Genet 2001, 59:171-177.
104. Friedlander Y., Lapidos T., Sinnreich R., Kark J.D. Genetic and environmental sources of QT interval variability in Israeli families: the kibbutz settlements family study. Clin Genet 1999, 56:200-209.
105. Singh J.P., Larson M.G., O'Donnell C.J., Tsuji H., Evans J.C., Levy D. Heritability of heart rate variability: the Framingham Heart Study. Circulation 1999, 99:2251-2254.
106. Busjahn A., Knoblauch H., Faulhaber H.D., Boeckel T., Rosenthal M., Uhlmann R., et al. QT interval is linked to 2 long-QT syndrome loci in normal subjects. Circulation 1999, 99:3161-3164.
107. Dalageorgou C., Ge D., Jamshidi Y., Nolte I.M., Riese H., Savelieva I., et al. Heritability of QT interval: how much is explained by genes for resting heart rate?. J Cardiovasc Electrophysiol 2008, 19:386-391.
108. Carter N., Snieder H., Jeffery S., Saumarez R., Varma C., Antoniades L., et al. QT interval in twins. J Hum Hypertens 2000, 14:389-390.
109. Jeff J.M., Brown-Gentry K., Buxbaum S.G., Sarpong D.F., Taylor H.A., George A.L., et al. SCN5A variation is associated with electrocardiographic traits in the Jackson Heart Study. Circ Cardiovasc Genet 2011, 4:139-144.