Overestimation of genetic risks owing to small sample sizes in cardiovascular studies

Clinical Genetics

Volumn 64, Issue 1, 2003, Pages 7-17

  Morgan, Thomas M ^a,b   Coffey, C S ^c   Krumholz, H M ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

^c UNIVERSITY OF ALABAMA SCHOOL OF MEDICINE   (United States)

Author keywords

Genetics; Meta analysis; Myocardial infarction; Risk factors

Indexed keywords

BLOOD CLOTTING FACTOR 5 LEIDEN; DIPEPTIDYL CARBOXYPEPTIDASE; GLYCOPROTEIN IIIA;

CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CONFIDENCE INTERVAL; DNA POLYMORPHISM; GENE DELETION; GENETIC PREDISPOSITION; GENETIC SCREENING; GENOTYPE; HEART INFARCTION; HUMAN; MEDLINE; META ANALYSIS; OUTCOMES RESEARCH; PRIORITY JOURNAL; PUBLICATION; REVIEW; RISK FACTOR; SAMPLE SIZE; THROMBOSIS;

CARDIOVASCULAR DISEASES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; POLYMORPHISM, GENETIC; RESEARCH DESIGN; RISK ASSESSMENT; SAMPLE SIZE;

EID: 0043133549     PISSN: 00099163     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1399-0004.2003.00088.x     Document Type: Review

References (106)

1. Ridker P, Stampfer M. Assessment of genetic markers for coronary thrombosis: promise and precaution. Lancet 1999: 353: 687-688.
2. Green FR, Watkins H. Genetic association studies in coronary disease. the cause of GPIIb-IIIa polymorphisms. Eur Heart J 1999: 20: 706-708.
3. Lalouel JM, Rohrwasser A. Power and replication in casecontrol studies. Am J Hypertens 2002: 15 (2 Part 1): 201-205.
4. Montori VM, Smieja M, Guyatt GH. Publication bias: a brief review for clinicians. Mayo Clin Proc 2000: 75: 1284-1288.
5. Molecular Diagnostics Laboratories. Cincinnati: Molecular Diagnostics Laboratories, 2002 [http://www.mdl-labs.com/ (accessed 5/3/02)].
6. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 2000: 20: 484-492.
7. Bray PF. Platelet glycoprotein polymorphisms as risk factors for thrombosis. Curr Opin Hematol 2000: 7: 284-289.
8. Keavney B, McKenzie C, Parish S et al. Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators. Lancet 2000: 355: 434-442.
9. Samani NJ, Thompson JR, O'Toole L, Channer K, Woods KL. A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation 1996: 94: 708-712.
10. Zoller B, Hillarp A, Berntorp E, Dahlback B. Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis. Annu Rev Med 1997: 48: 45-58.
11. Zoller B, Dahlback B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994: 343: 1536-1538.
12. Bertina RM, Koeleman BP, Koster T et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994: 369: 64-67.
13. Altmann C, Liu R, Farber K et al. Association of the platelet fibrinogen receptor polymorphism P1A1/PLA2 in diabetic and non-diabetic patients with acute ischemic events. Eur Heart J 1998: 19 (Suppl.): 107.
14. Anderson JL, King GJ, Bair TL et al. Associations between a polymorphism in the gene encoding glycoprotein IIIa and myocardial infarction or coronary artery disease. J Am Coll Cardiol 1999: 33: 727-733.
15. Ardissino D, Mannucci PM, Merlini PA et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999: 94: 46-51.
16. Bottiger C, Kastrati A, Koch W et al. HPA-1 and HPA-3 polymorphisms of the platelet fibrinogen receptor and coronary artery disease and myocardial infarction. Thromb Haemost 2000: 83: 559-562.
17. Brscic E, Bergerone S, Gagnor A et al. Acute myocardial infarction in young adults: prognostic role of angiotensin-converting enzyme, angiotensin II type I receptor, apolipoprotein E, endothelial constitutive nitric oxide synthase, and glycoprotein IIIa genetic polymorphisms at medium-term follow-up. Am Heart J 2000: 139: 979-984.
18. Carter AM, Ossei-Gerning N, Grant PJ. Platelet glycoprotein IIIa P1A polymorphism and myocardial infarction. N Engl J Med 1996: 335: 1072-1073 [discussion 1073-1074].
19. Carter AM, Ossei-Gerning N, Wilson IJ, Grant PJ. Association of the platelet P1 (A) polymorphism of glycoprotein IIb/IIIa and the fibrinogen Bbeta 448 polymorphism with myocardial infarction and extent of coronary artery disease. Circulation 1997: 96: 1424-1431.
20. Corral J, Gonzalez-Conejero R, Rivera J, Iniesta JA, Lozano ML, Vicente V. HPA-1 genotype in arterial thrombosis - role of HPA-1b polymorphism in platelet function. Blood Coagul Fibrinol 1997: 8: 284-290.
21. Durante-Mangoni E, Davies GJ, Ahmed N, Ruggiero G, Tuddenham EG. Coronary thrombosis and the platelet glycoprotein IIIA gene PLA2 polymorphism. Thromb Haemost 1998: 80: 218-219.
22. Gardemann A, Humme J, Stricker J et al. Association of the platelet glycoprotein IIIa P1A1/A2 gene polymorphism to coronary artery disease but not to nonfatal myocardial infarction in low risk patients. Thromb Haemost 1998: 80: 214-217.
23. Goodall AH, Curzen N, Panesar M et al. Increased binding of fibrinogen to glycoprotein IIIa-proline33 (HPA-1b, P1A2, Zwb) positive platelets in patients with cardiovascular disease. Eur Heart J 1999: 20: 742-747.
24. Hato T, Minamoto Y, Fukuyama T, Fujita S. Polymorphisms of HPA-1 through 6 on platelet membrane glycoprotein receptors are not a genetic risk factor for myocardial infarction in the Japanese population. Am J Cardiol 1997: 80: 1222-1224.
25. Herrmann SM, Poirier O, Marques-Vidal P et al. The Leu33/Pro polymorphism (P1A1/P1A2) of the glycoprotein IIIa (GPIIIa) receptor is not related to myocardial infarction in the ECTIM Study. Etude Cas-Temoins L'Infarctus du Myocarde. Thromb Haemost 1997: 77: 1179-1181.
26. Hooper WC, Lally C, Austin H et al. The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans. Chest 1999: 116: 880-886.
27. Joven J, Simo JM, Vilella E et al. Lipoprotein (a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction. Atherosclerosis 1998: 140: 155-159.
28. Kekomaki S, Hamalainen L, Kauppinen-Makelin R, Palomaki H, Kaste M, Kontula K. Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke. J Cardiovasc Risk 1999: 6: 13-17.
29. Kettling C, Kastrati A, Koch W et al. Is P1A polymorphism of platelet glycoprotein IIIa associated with acute myocardial infarction? Eur Heart J 1998: 19 (Suppl.): 360.
30. Mamotte CD, van Bockxmeer FM, Taylor RR. PIa1/a2 polymorphism of glycoprotein IIIa and risk of coronary artery disease and restenosis following coronary angioplasty. Am J Cardiol 1998: 82: 13-16.
31. Marian AJ, Brugada R, Kleiman NS. Platelet glycoprotein IIIa P1A polymorphism and myocardial infarction. N Engl J Med 1996: 335: 1071-1072 [discussion 1073-1074].
32. Mikkelsson J, Perola M, Laippala P, Penttila A, Karhunen PJ. Glycoprotein IIIa P1 (A1/A2) polymorphism and sudden cardiac death. J Am Coll Cardiol 2000: 36: 1317-1323.
33. Osborn SV, Hampton KK, Smillie D, Channer KS, Daly ME. Platelet glycoprotein IIIa gene polymorphism and myocardial infarction. Lancet 1996: 348: 1309-1310.
34. Pastinen T, Perola M, Niini P et al. Array-based multiplex analysis of candidate genes reveals two independent and additive genetic risk factors for myocardial infarction in the Finnish population. Hum Mol Genet 1998: 7: 1453-1462.
35. Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet 1997: 349: 385-388.
36. Samani NJ, Lodwick D. Glycoprotein IIIa polymorphism and risk of myocardial infarction. Cardiovasc Res 1997: 33: 693-697.
37. Scaglione L, Bergerone S, Gaschino G et al. Lack of relationship between the P1A1/P1A2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction. Eur J Clin Invest 1998: 28: 385-388.
38. Senti M, Aubo C, Bosch M et al. Platelet glycoprotein IIb/IIIa genetic polymorphism is associated with plasma fibrinogen levels in myocardial infarction patients. The REGICOR Investigators. Clin Biochem 1998: 31: 647-651.
39. Weiss EJ, Bray PF, Tayback M et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996: 334: 1090-1094.
40. Zotz RB, Winkelmann BR, Nauck M et al. Polymorphism of platelet membrane glycoprotein IIIa: human platelet antigen 1b (HPA-1b/P1A2) is an inherited risk factor for premature myocardial infarction in coronary artery disease. Thromb Haemost 1998: 79: 731-735.
41. Agerholm-Larsen B, Tybjaerg-Hansen A, Frikke-Schmidt R, Gronholdt ML, Jensen G, Nordestgaard BG. ACE gene polymorphism as a risk factor for ischemic cerebrovascular disease. Ann Intern Med 1997: 127: 346-355.
42. Ahnve S, Flodin T, Berglund L, Eggertson G, Sylven C. Angiotensin converting enzyme gene polymorphism in acute myocardial infarction patients. J Am Coll Cardiol 1995: 25: 276A.
43. Akar N, Aras O, Omurlu K, Cin S. Deletion polymorphism at the angiotensin-converting enzyme gene in Turkish patients with coronary artery disease. Scand J Clin Lab Invest 1998: 58: 491-495.
44. Anderson JL, Carlquist JF, King GJ et al. Angiotensin-converting enzyme genotypes and risk for myocardial infarction in women. J Am Coll Cardiol 1998: 31: 790-796.
45. Arbustini E, Grasso M, Fasani R et al. Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction. Br Heart J 1995: 74: 584-591.
46. Arca M, Pannitteri G, Campagna F et al. Angiotensin-converting enzyme gene polymorphism is not associated with coronary atherosclerosis and myocardial infarction in a sample of Italian patients. Eur J Clin Invest 1998: 28: 485-490.
47. Batalla A, Alvarez R, Reguero JR et al. Synergistic effect between apolipoprotein E and angiotensinogen gene polymorphisms in the risk for early myocardial infarction. Clin Chem 2000: 46: 1910-1915.
48. Biggart S, Chin D, Fauchon M et al. Association of genetic polymorphisms in the ACE, ApoE, and TGF beta genes with early onset ischemic heart disease. Clin Cardiol 1998: 21: 831-836.
49. Beohar N, Damaraju S, Prather A et al. Angiotensin-I converting enzyme genotype DD is a risk factor for coronary artery disease. J Invest Med 1995: 43: 275-280.
50. Bogaty P, Robitaille NM, Solymoss S et al. Atherogenic, hemostatic, and other potential risk markers in subjects with previous isolated myocardial infarction compared with long-standing uncomplicated stable angina. Am Heart J 1998: 136: 884-893.
51. Bohn M, Berge KE, Bakken A, Erikssen J, Berg K. Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and myocardial infarction. Clin Genet 1993: 44: 292-297.
52. Cambien F, Poirier O, Lecerf L et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992: 359: 641-644.
53. Cambien F, Costerousse O, Tiret L et al. Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction. Circulation 1994: 90: 669-676.
54. Chiang FT, Lai ZP, Chern TH et al. Lack of association between angiotensin-converting enzyme gene polymorphism and coronary heart disease in a Chinese population. Jpn Heart J 1997: 38: 227-236.
55. Ferrieres J, Ruidavets JB, Fauvel J et al. Angiotensin I-converting enzyme gene polymorphism in a low-risk European population for coronary artery disease. Atherosclerosis 1999: 142: 211-216.
56. Friedl W, Krempler F, Paulweber B, Pichler M, Sandhofer F. A deletion polymorphism in the angiotensin converting enzyme gene is not associated with coronary heart disease in an Austrian population. Atherosclerosis 1995: 112: 137-143.
57. Fujimura T, Yokota M, Kato S et al. Lack of association of angiotensin converting enzyme gene polymorphism or serum enzyme activity with coronary artery disease in Japanese subjects. Am J Hypertens 1997: 10 (12 Part 1): 1384-1390.
58. Gardemann A, Weiss T, Schwartz O et al. Gene polymorphism, but not catalytic activity, of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients. Circulation 1995: 92: 2796-2799.
59. Gardemann A, Fink M, Stricker J et al. ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals. Atherosclerosis 1998: 139: 153-159.
60. Iwai N, Tamaki S, Ohmichi N, Kinoshita M. The II genotype of the angiotensin-converting enzyme gene delays the onset of acute coronary syndromes. Arterioscler Thromb Vasc Biol 1997: 17: 1730-1733.
61. Jamieson A, Murdoch D, Inglis G. ACE genotype is not a risk factor for myocardial infarction under 45 years of age. Br Heart J 1995: 73 (Suppl. 3): P186.
62. Kamitani A, Rakugi H, Higaki J et al. Enhanced predictability of myocardial infarction in Japanese by combined genotype analysis. Hypertension 1995: 25: 950-953.
63. Katsuya T, Koike G, Yee TW et al. Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. Lancet 1995: 345: 1600-1603.
64. Kee F, Morrison C, Poirier O et al. Angiotensin II type-I receptor and ACE polymorphisms and risk of myocardial infarction in men and women. Eur J Clin Invest 2000: 30: 1076-1082.
65. Ko YL, Ko YS, Wang SM et al. Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese. Hum Genet 1997: 100: 210-214.
66. Leatham E, Barley J, Redwood S et al. Angiotensin-1 converting enzyme (ACE) polymorphism in patients presenting with myocardial infarction or unstable angina. J Hum Hypertens 1994: 8: 635-638.
67. Lindpaintner K, Pfeffer MA, Kreutz R et al. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995: 332: 706-711.
68. Ludwig E, Corneli PS, Anderson JL, Marshall HW, Lalouel JM, Ward RH. Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis. Circulation 1995: 91: 2120-2124.
69. Ludwig EH, Borecki IB, Ellison RC et al. Associations between candidate loci angiotensin-converting enzyme and angiotensinogen with coronary heart disease and myocardial infarction: the NHLBI Family Heart Study. Ann Epidemiol 1997: 7: 3-12.
70. Mansur AP, Annicchino-Bizzacchi J, Favarato D, Avakian SD, Cesar LA, Ramires JA. Angiotensin-converting enzyme and apolipoproteins genes polymorphism in coronary artery disease. Clin Cardiol 2000: 23: 335-340.
71. Nakauchi Y, Suehiro T, Yamamoto M et al. Significance of angiotensin I-converting enzyme and angiotensin II type 1 receptor gene polymorphisms as risk factors for coronary heart disease. Atherosclerosis 1996: 125: 161-169.
72. Pfohl M, Athanasiadis A, Koch M et al. Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is associated with coronary artery plaque calcification as assessed by intravascular ultrasound. J Am Coll Cardiol 1998: 31: 987-991.
73. Samani NJ, O'Toole L, Martin D et al. Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of and prognosis after myocardial infarction. J Am Coll Cardiol 1996: 28: 338-344.
74. Schuster H, Wienker TF, Stremmler U, Noll B, Steinmetz A, Luft FC. An angiotensin-converting enzyme gene variant is associated with acute myocardial infarction in women but not in men. Am J Cardiol 1995: 76: 601-603.
75. Sigusch HH, Vogt S, Gruber U et al. Angiotensin-I-converting enzyme DD genotype is a risk factor of coronary artery disease. Scand J Clin Lab Invest 1997: 57: 127-132.
76. Takahashi K, Nakamura H, Kubota I, Takahashi N, Tomoike H. Association of ACE gene polymorphisms with coronary artery disease in a northern area of Japan. Jpn Heart J 1995: 36: 557-564.
77. van Bockxmeer FM, Mamotte CD, Burke V, Taylor RR. Angiotensin-converting enzyme gene polymorphism and premature coronary heart disease. Clin Sci (Lond) 2000: 99: 247-251.
78. Wang XL, McCredie RM, Wilcken DE. Genotype distribution of angiotensin-converting enzyme polymorphism in Australian healthy and coronary populations and relevance to myocardial infarction and coronary artery disease. Arterioscler Thromb Vasc Biol 1996: 16: 115-119.
79. Winkelmann BR, Nauck M, Klein B et al. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with increased plasma angiotensin-converting enzyme activity but not with increased risk for myocardial infarction and coronary artery disease. Ann Intern Med 1996: 125: 19-25.
80. Adamczuk Y, Iglesias Varela ML, Forastiero R et al. Factor V Leiden and prothrombin G20210A variant are risk factors for venous thromboembolism in the Argentinean population. Thromb Haemost 2000: 83: 509-510.
81. Alhenc-Gelas M, Arnaud E, Nicaud V et al. Venous thromboembolic disease and the prothrombin, methylene tetrahydrofolate reductase and factor V genes. Thromb Haemost 1999: 81: 506-510.
82. Baglin TP, Brown K, Williamson D, Baker P, Luddington R. Relative risk of pulmonary embolism and deep vein thrombosis in association with the factor V Leiden mutation in a United Kingdom population. Thromb Haemost 1997: 77: 1219.
83. Campos M, Morais S, Sousa S et al. Prevalence of FV Leiden mutation in venous and arterial thrombosis. Thromb Haemost 1997: 77 (Suppl.): 308.
84. Cattaneo M, Tsai MY, Bucciarelli P et al. A common mutation in the methylenetetrahydrofolate reductase gene (C677T) increases the risk for deep-vein thrombosis in patients with mutant factor V (factor V. Q506). Arterioscler Thromb Vasc Biol 1997: 17: 1662-1666.
85. Cattaneo M, Chantarangkul V, Taioli E, Santos JH, Tagliabue L. The G20210A mutation of the prothrombin gene in patients with previous first episodes of deep-vein thrombosis: prevalence and association with factor V G1691A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels. Thromb Res 1999: 93: 1-8.
86. de Moerloose P, Reber G, Perrier A, Perneger T, Bounameaux H. Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism. Br J Haematol 2000: 110: 125-129.
87. Faioni EM, Franchi F, Bucciarelli P et al. Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden). Blood 1999: 94: 3062-3066.
88. Hillarp A, Zoller B, Svensson PJ, Dahlback B. The 20210 A allele of the prothrombin gene is a common risk factor among Swedish outpatients with verified deep venous thrombosis. Thromb Haemost 1997: 78: 990-992.
89. Leroyer C, Mercier B, Escoffre M, Ferec C, Mottier D. Factor V Leiden prevalence in venous thromboembolism patients. Ghest 1997: 111: 1603-1606.
90. Leroyer C, Mercier B, Oger E et al. Prevalence of 20210 A allele of the prothrombin gene in venous thromboembolism patients. Thromb Haemost 1998: 80: 49-51.
91. Ma DD, Aboud MR, Williams BG, Isbister JP. Activated protein C resistance (APC) and inherited factor V (FV) missense mutation in patients with venous and arterial thrombosis in a haematology clinic. Aust N Z J Med 1995: 25: 151-154.
92. Manten B, Westendorp RG, Koster T, Reitsma PH, Rosendaal FR. Risk factor profiles in patients with different clinical manifestations of venous thromboembolism: a focus on the factor V Leiden mutation. Thromb Haemost 1996: 76: 510-513.
93. Margaglione M, Brancaccio V, Giuliani N et al. Increased risk for venous thrombosis in carriers of the prothrombin G→A20210 gene variant. Ann Intern Med 1998: 129: 89-93.
94. Margaglione M, Brancaccio V, De Lucia D et al. Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism. Chest 2000: 118: 1405-1411.
95. Olafsson I, Hjaltadottir S, Onundarson PT, Porarinsdottir R, Haraldsdottir V. Prevalence of factor V(Q506) and prothrombin 20210 A mutations in an apparently healthy Icelandic population and patients suffering from venous thrombosis. Thromb Haemost 1998: 79: 685-686.
96. Ordonez AJ, Carreira JM, Alvarez CR, Rodriguez JM, Alvarez MV, Coto E. Comparison of the risk of pulmonary embolism and deep vein thrombosis in the presence of factor V Leiden or prothrombin G20210A. Thromb Haemost 2000: 83: 352-354.
97. Renner W, Koppel H, Hoffmann C et al. Prothrombin G20210A, factor V Leiden, and factor XIII Va134Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria. Thromb Res 2000: 99: 35-39
98. Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 1995: 332: 912-917.
99. Rodeghiero F, Tosetto A. Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism. Ann Intern Med 1999: 130: 643-650.
100. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995: 85: 1504-1508.
101. Svensson PJ, Zoller B, Mattiasson I, Dahlback B. The factor VR506Q mutation causing APC resistance is highly prevalent amongst unselected outpatients with clinically suspected deep venous thrombosis. J Intern Med 1997: 241: 379-385.
102. Bounameaux H. Factor V Leiden paradox: risk of deep-vein thrombosis but not of pulmonary embolism. Lancet 2000: 356: 182-183.
103. Thornton A, Lee P. Publication bias in meta-analysis. its causes and consequences. J Clin Epidemiol 2000: 53: 207-216.
104. Deeks J, Altman D, Bradburn M. Statistical methods for examining heterogeneity and combining results from several studies in a meta-analysis. In: Altman D, ed. Systematic Reviews and Healthcare: Meta-Analysis in Context. London: BMJ Publications, 2001.
105. Berkey CS, Hoaglin DC, Antczak-Bouckoms A, Mosteller F, Colditz GA. Meta-analysis of multiple outcomes by regression with random effects. Stat Med 1998: 17: 2537-2550.
106. Halpern SD, Karlawish JH, Berlin JA. The continuing unethical conduct of underpowered clinical trials. JAMA 2002: 288: 358-362.