Download PDF
Semin Thromb Hemost 2016; 42(08): 821-832
DOI: 10.1055/s-0036-1593543
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Epidemiology of Familial Aggregation of Venous Thromboembolism

Bengt Zöller
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Xinjun Li
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Henrik Ohlsson
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Jianguang Ji
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Ashfaque A. Memon
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Peter J. Svensson
2   Department of Coagulation Disorders, Skåne University Hospital, Malmö, Sweden
,
Karolina Palmér
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Björn Dahlbäck
3   Department of Translational Medicine, Lund University, The Wallenberg Laboratory, Malmö, Sweden
,
Jan Sundquist
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
,
Kristina Sundquist
1   Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

Publication Date:
20 October 2016 (online)

    Permissions and Reprints

Abstract

Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characteristics of complex traits. The family history of VTE in first-degree relatives is associated with a two to three times increased familial relative risk (FRR). The FRR of VTE is higher in younger individuals, increases with a number of affected relatives, decreases as the familial relationship becomes more distant, increases with severity (unprovoked), and exhibits slightly stronger male transmission (Carter effect). High FRR is observed in individuals with two or more affected siblings (FRR > 50). Because familial aggregation represents the sum of shared family environmental and genetic factors, one should not assume that evidence of familial aggregation implies genetic effects. However, studies in twins, extended families, adoptees, and spouses indicate a weak involvement of shared environmental factors to the familial aggregation of VTE. Moreover, familial aggregation of VTE fulfills the Hill's criteria for causation. In conclusion, familial aggregation of VTE signals a clinically relevant inherent predisposition for VTE.

Keywords

venous thrombosis - venous thromboembolism - genetics - epidemiology - thrombophilia
 

  • References

  • 1 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353 (9159) 1167-1173
    CrossrefPubMedGoogle Scholar
  • 2 Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994; 265 (5181) 2037-2048
    CrossrefPubMedGoogle Scholar
  • 3 Burton PR, Tobin MD, Hopper JL. Key concepts in genetic epidemiology. Lancet 2005; 366 (9489) 941-951
    CrossrefPubMedGoogle Scholar
  • 4 Risch N. The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches. Cancer Epidemiol Biomarkers Prev 2001; 10 (7) 733-741
    PubMedGoogle Scholar
  • 5 Briggs JB. Recurring phlebitis of obscure origins. Johns Hopkins Hosp Bull 1905; 16: 228-233
    PubMedGoogle Scholar
  • 6 Jordan FL, Nandorff A. The familial tendency in thrombo-embolic disease. Acta Med Scand 1956; 156 (4) 267-275
    CrossrefPubMedGoogle Scholar
  • 7 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-530
    PubMedGoogle Scholar
  • 8 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68 (5) 1370-1373
    CrossrefPubMedGoogle Scholar
  • 9 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311 (24) 1525-1528
    CrossrefPubMedGoogle Scholar
  • 10 Comp PC, Nixon RR, Cooper MR, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74 (6) 2082-2088
    CrossrefPubMedGoogle Scholar
  • 11 Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6) 1297-1300
    CrossrefPubMedGoogle Scholar
  • 12 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A 1993; 90 (3) 1004-1008
    CrossrefPubMedGoogle Scholar
  • 13 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330 (8) 517-522
    CrossrefPubMedGoogle Scholar
  • 14 Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci U S A 1994; 91 (4) 1396-1400
    CrossrefPubMedGoogle Scholar
  • 15 Bertina RM, Koeleman BP, Koster T , et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369 (6475) 64-67
    CrossrefPubMedGoogle Scholar
  • 16 Sun X, Evatt B, Griffin JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83 (11) 3120-3125
    PubMedGoogle Scholar
  • 17 Voorberg J, Roelse J, Koopman R , et al. Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V. Lancet 1994; 343 (8912) 1535-1536
    CrossrefPubMedGoogle Scholar
  • 18 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343 (8912) 1536-1538
    CrossrefPubMedGoogle Scholar
  • 19 Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94 (6) 2521-2524
    CrossrefPubMedGoogle Scholar
  • 20 Koeleman BP, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84 (4) 1031-1035
    PubMedGoogle Scholar
  • 21 Zöller B, Berntsdotter A, García de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S. Blood 1995; 85 (12) 3518-3523
    PubMedGoogle Scholar
  • 22 Zöller B, García de Frutos P, Hillarp A, Dahlbäck B. Thrombophilia as a multigenic disease. Haematologica 1999; 84 (1) 59-70
    PubMedGoogle Scholar
  • 23 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88 (10) 3698-3703
    CrossrefPubMedGoogle Scholar
  • 24 Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008; 112 (1) 19-27
    CrossrefPubMedGoogle Scholar
  • 25 Mannucci PM, Franchini M. Classic thrombophilic gene variants. Thromb Haemost 2015; 114 (5) 885-889
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Morange PE, Suchon P, Trégouët DA. Genetics of Venous Thrombosis: update in 2015. Thromb Haemost 2015; 114 (5) 910-919
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Reitsma PH. Genetics in thrombophilia. An update. Hamostaseologie 2015; 35 (1) 47-51
    PubMedGoogle Scholar
  • 28 Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med 2009; 169 (6) 610-615
    CrossrefPubMedGoogle Scholar
  • 29 Cosmi B, Legnani C, Bernardi F, Coccheri S, Palareti G. Value of family history in identifying women at risk of venous thromboembolism during oral contraception: observational study. BMJ 2001; 322 (7293) 1024-1025
    CrossrefPubMedGoogle Scholar
  • 30 Cosmi B, Legnani C, Bernardi F, Coccheri S, Palareti G. Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception. Arch Intern Med 2003; 163 (9) 1105-1109
    CrossrefPubMedGoogle Scholar
  • 31 Aznar J, Mira Y, Vayá A, Ferrando F, Villa P. Is family history sufficient to identify women with risk of venous thromboembolism before commencing the contraceptive pill?. Clin Appl Thromb Hemost 2002; 8 (2) 139-141
    CrossrefPubMedGoogle Scholar
  • 32 van Sluis GL, Söhne M, El Kheir DY, Tanck MW, Gerdes VE, Büller HR. Family history and inherited thrombophilia. J Thromb Haemost 2006; 4 (10) 2182-2187
    CrossrefPubMedGoogle Scholar
  • 33 Dietrich JE, Hertweck SP, Perlman SE. Efficacy of family history in determining thrombophilia risk. J Pediatr Adolesc Gynecol 2007; 20 (4) 221-224
    CrossrefPubMedGoogle Scholar
  • 34 Briët E, van der Meer FJ, Rosendaal FR, Houwing-Duistermaat JJ, van Houwelingen HC. The family history and inherited thrombophilia. Br J Haematol 1994; 87 (2) 348-352
    CrossrefPubMedGoogle Scholar
  • 35 Vagdatli E, Serafimidou O, Pantziarela E, Tsikopoulou F, Mitsopoulou K, Papoutsi A. Prevalence of thrombophilia in asymptomatic individuals with a family history of thrombosis. Hippokratia 2013; 17 (4) 359-362
    PubMedGoogle Scholar
  • 36 Grimes DA, Stuart GS, Levi EE. Screening women for oral contraception: can family history identify inherited thrombophilias?. Obstet Gynecol 2012; 120 (4) 889-895
    CrossrefPubMedGoogle Scholar
  • 37 Dumenco LL, Blair AJ, Sweeney JD. The results of diagnostic studies for thrombophilia in a large group of patients with a personal or family history of thrombosis. Am J Clin Pathol 1998; 110 (5) 673-682
    CrossrefPubMedGoogle Scholar
  • 38 Ruud E, Holmstrøm H, Brosstad F, Wesenberg F. Diagnostic value of family histories of thrombosis to identify children with thrombophilia. Pediatr Hematol Oncol 2005; 22 (6) 453-462
    CrossrefPubMedGoogle Scholar
  • 39 Hill AB. The environment and disease: association or causation?. Proc R Soc Med 1965; 58: 295-300
    PubMedGoogle Scholar
  • 40 Noboa S, Le Gal G, Lacut K , et al; EDITH Collaborative Study Group. Family history as a risk factor for venous thromboembolism. Thromb Res 2008; 122 (5) 624-629
    CrossrefPubMedGoogle Scholar
  • 41 Dowling NF, Austin H, Dilley A, Whitsett C, Evatt BL, Hooper WC. The epidemiology of venous thromboembolism in Caucasians and African-Americans: the GATE Study. J Thromb Haemost 2003; 1 (1) 80-87
    CrossrefPubMedGoogle Scholar
  • 42 Thomas DC. Statistical Methods in Genetic Epidemiology. New York, NY: Oxford University Press; 2004
    Google Scholar
  • 43 Larsen TB, Sørensen HT, Skytthe A, Johnsen SP, Vaupel JW, Christensen K. Major genetic susceptibility for venous thromboembolism in men: a study of Danish twins. Epidemiology 2003; 14 (3) 328-332
    PubMedGoogle Scholar
  • 44 Zöller B, Li X, Sundquist J, Sundquist K. Familial transmission of venous thromboembolism: a cohort study of 80 214 Swedish adoptees linked to their biological and adoptive parents. Circ Cardiovasc Genet 2014; 7 (3) 296-303
    CrossrefPubMedGoogle Scholar
  • 45 Kerber RA. Method for calculating risk associated with family history of a disease. Genet Epidemiol 1995; 12 (3) 291-301
    CrossrefPubMedGoogle Scholar
  • 46 Rice TK, Borecki IB. Familial resemblance and heritability. Adv Genet 2001; 42: 35-44
    PubMedGoogle Scholar
  • 47 Zöller B, Ohlsson H, Sundquist J, Sundquist K. Familial risk of venous thromboembolism in first-, second- and third-degree relatives: a nationwide family study in Sweden. Thromb Haemost 2013; 109 (3) 458-463
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Souto JC, Almasy L, Borrell M , et al. Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic Analysis of Idiopathic Thrombophilia. Am J Hum Genet 2000; 67 (6) 1452-1459
    CrossrefPubMedGoogle Scholar
  • 49 Heit JA, Phelps MA, Ward SA, Slusser JP, Petterson TM, De Andrade M. Familial segregation of venous thromboembolism. J Thromb Haemost 2004; 2 (5) 731-736
    CrossrefPubMedGoogle Scholar
  • 50 Lawler DA, Mishra GD. Why family matters: an introduction. In: Lawlor DA, Mishra GD, eds. Family Matters: Designing, Analysing and Understanding Family-Based Studies in Life-Course Epidemiology. New York, NY: Oxford University Press; 2009: 1-9
    CrossrefGoogle Scholar
  • 51 Zöller B, Li X, Sundquist J, Sundquist K. Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden. Circulation 2011; 124 (9) 1012-1020
    CrossrefPubMedGoogle Scholar
  • 52 Fedak KM, Bernal A, Capshaw ZA, Gross S. Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology. Emerg Themes Epidemiol 2015; 12: 14
    CrossrefPubMedGoogle Scholar
  • 53 Tosetto A, Frezzato M, Rodeghiero F. Prevalence and risk factors of non-fatal venous thromboembolism in the active population of the VITA Project. J Thromb Haemost 2003; 1 (8) 1724-1729
    CrossrefPubMedGoogle Scholar
  • 54 Lidegaard Ø, Edström B, Kreiner S. Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception 2002; 65 (3) 187-196
    CrossrefPubMedGoogle Scholar
  • 55 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Old and new risk factors for upper extremity deep venous thrombosis. J Thromb Haemost 2005; 3 (11) 2471-2478
    CrossrefPubMedGoogle Scholar
  • 56 Mili FD, Hooper WC, Lally C, Austin H. The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks. Thromb Res 2011; 127 (4) 309-316
    CrossrefPubMedGoogle Scholar
  • 57 Sonnevi K, Bergendal A, Adami J, Lärfars G, Kieler H. Self-reported family history in estimating the risk of hormone, surgery and cast related VTE in women. Thromb Res 2013; 132 (2) 164-169
    CrossrefPubMedGoogle Scholar
  • 58 Rojnuckarin P, Uaprasert N, Vajragupta L, Numkarunarunrote N, Tanpowpong N, Sutcharitchan P. Risk factors for symptomatic venous thromboembolism in Thai hospitalised medical patients. Thromb Haemost 2011; 106 (6) 1103-1108
    Article in Thieme ConnectPubMedGoogle Scholar
  • 59 Bosson JL, Pouchain D, Bergmann JF ; ETAPE Study Group. A prospective observational study of a cohort of outpatients with an acute medical event and reduced mobility: incidence of symptomatic thromboembolism and description of thromboprophylaxis practices. J Intern Med 2006; 260 (2) 168-176
    CrossrefPubMedGoogle Scholar
  • 60 Spannagl M, Heinemann LA, Dominh T, Assmann A, Schramm W, Schürmann R. Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: a community-based cohort study. Thromb J 2005; 3: 8
    CrossrefPubMedGoogle Scholar
  • 61 Sørensen HT, Riis AH, Diaz LJ, Andersen EW, Baron JA, Andersen PK. Familial risk of venous thromboembolism: a nationwide cohort study. J Thromb Haemost 2011; 9 (2) 320-324
    CrossrefPubMedGoogle Scholar
  • 62 Zöller B, Li X, Sundquist J, Sundquist K. A nationwide family study of pulmonary embolism: identification of high risk families with increased risk of hospitalized and fatal pulmonary embolism. Thromb Res 2012; 130 (2) 178-182
    CrossrefPubMedGoogle Scholar
  • 63 Zöller B, Li X, Sundquist J, Sundquist K. Parental history and venous thromboembolism: a nationwide study of age-specific and sex-specific familial risks in Sweden. J Thromb Haemost 2011; 9 (1) 64-70
    CrossrefPubMedGoogle Scholar
  • 64 Khoury MJ, Beaty TH, Liang KY. Can familial aggregation of disease be explained by familial aggregation of environmental risk factors?. Am J Epidemiol 1988; 127 (3) 674-683
    CrossrefPubMedGoogle Scholar
  • 65 Zöller B, Li X, Sundquist J, Sundquist K. Determination of age-specific and sex-specific familial risks for the different manifestations of venous thromboembolism: a nationwide family study in Sweden. Thromb Haemost 2011; 106 (1) 102-112
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Zöller B, Li X, Sundquist J, Sundquist K. Familial risks of unusual forms of venous thrombosis: a nationwide epidemiological study in Sweden. J Intern Med 2011; 270 (2) 158-165
    CrossrefPubMedGoogle Scholar
  • 67 Zöller B, Li X, Sundquist J, Sundquist K. Shared familial aggregation of susceptibility to different manifestations of venous thromboembolism: a nationwide family study in Sweden. Br J Haematol 2012; 157 (1) 146-148
    CrossrefPubMedGoogle Scholar
  • 68 Zöller B, Ji J, Sundquist J, Sundquist K. Venous thromboembolism and varicose veins share familial susceptibility: a nationwide family study in Sweden. J Am Heart Assoc 2014; 3 (4) e000850
    CrossrefPubMedGoogle Scholar
  • 69 Zöller B, Li X, Sundquist J, Sundquist K. A nationwide family study of venous thromboembolism and risk of arterial vascular disease. Heart 2016; 102 (16) 1315-1321
    CrossrefPubMedGoogle Scholar
  • 70 Lind C, Enga KF, Mathiesen EB, Njølstad I, Brækkan SK, Hansen JB. Family history of myocardial infarction and cause-specific risk of myocardial infarction and venous thromboembolism: the Tromsø Study. Circ Cardiovasc Genet 2014; 7 (5) 684-691
    CrossrefPubMedGoogle Scholar
  • 71 Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB. Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study. J Thromb Haemost 2008; 6 (11) 1851-1857
    CrossrefPubMedGoogle Scholar
  • 72 Mili FD, Hooper WC, Lally C, Austin H. Family history of myocardial infarction is a risk factor for venous thromboembolism among whites but not among blacks. Clin Appl Thromb Hemost 2013; 19 (4) 410-417
    CrossrefPubMedGoogle Scholar
  • 73 Zöller B, Li X, Sundquist J, Sundquist K. Venous thromboembolism does not share strong familial susceptibility with coronary heart disease: a nationwide family study in Sweden. Eur Heart J 2011; 32 (22) 2800-2805
    CrossrefPubMedGoogle Scholar
  • 74 Zöller B, Li X, Ohlsson H, Sundquist J, Sundquist K. Venous thromboembolism does not share strong familial susceptibility with ischemic stroke: a nationwide family study in Sweden. Circ Cardiovasc Genet 2011; 4 (5) 484-490
    CrossrefPubMedGoogle Scholar
  • 75 Zöller B, Ji J, Sundquist J, Sundquist K. Familial risk factors shared by venous thromboembolism and cancer: a nationwide epidemiological study of Swedish families. Thromb Res 2011; 128 (2) 141-148
    CrossrefPubMedGoogle Scholar
  • 76 Zöller B, Li X, Sundquist J, Sundquist K. Venous thromboembolism does not share strong familial susceptibility with pre-eclampsia/eclampsia: a nationwide family study in Sweden. BJOG 2013; 120 (10) 1200-1206
    CrossrefPubMedGoogle Scholar
  • 77 Zöller B, Li X, Sundquist J, Sundquist K. Venous thromboembolism does not share familial susceptibility with retinal vascular occlusion or glaucoma: a nationwide family study. J Thromb Thrombolysis 2016; ; In press
    PubMedGoogle Scholar
  • 78 Bruzelius M, Strawbridge RJ, Trégouët DA , et al. Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism. Thromb Res 2014; 134 (2) 426-432
    CrossrefPubMedGoogle Scholar
  • 79 Prandoni P, Prins MH, Ghirarduzzi A , et al. Family history of venous thrombosis or sudden death as a risk factor for venous thromboembolism. Thromb Haemost 2012; 107 (6) 1191-1192
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW. Pleiotropy in complex traits: challenges and strategies. Nat Rev Genet 2013; 14 (7) 483-495
    CrossrefPubMedGoogle Scholar
  • 81 Couturaud F, Leroyer C, Tromeur C , et al. Factors that predict thrombosis in relatives of patients with venous thromboembolism. Blood 2014; 124 (13) 2124-2130
    CrossrefPubMedGoogle Scholar
  • 82 Couturaud F, Leroyer C, Julian JA , et al. Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism. Chest 2009; 136 (6) 1537-1545
    CrossrefPubMedGoogle Scholar
  • 83 Allaart CF, Poort SR, Rosendaal FR, Reitsma PH, Bertina RM, Briët E. Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect. Lancet 1993; 341 (8838) 134-138
    CrossrefPubMedGoogle Scholar
  • 84 Hron G, Eichinger S, Weltermann A , et al. Family history for venous thromboembolism and the risk for recurrence. Am J Med 2006; 119 (1) 50-53
    CrossrefPubMedGoogle Scholar
  • 85 Gauthier K, Kovacs MJ, Wells PS, Le Gal G, Rodger M ; REVERSE investigators. Family history of venous thromboembolism (VTE) as a predictor for recurrent VTE in unprovoked VTE patients. J Thromb Haemost 2013; 11 (1) 200-203
    CrossrefPubMedGoogle Scholar
  • 86 Zöller B, Ohlsson H, Sundquist J, Sundquist K. Family history of venous thromboembolism (VTE) and risk of recurrent hospitalization for VTE: a nationwide family study in Sweden. J Thromb Haemost 2014; 12 (3) 306-312
    CrossrefPubMedGoogle Scholar
  • 87 Sundquist K, Sundquist J, Svensson PJ, Zöller B, Memon AA. Role of family history of venous thromboembolism and thrombophilia as predictors of recurrence: a prospective follow-up study. J Thromb Haemost 2015; 13 (12) 2180-2186
    CrossrefPubMedGoogle Scholar
  • 88 Bruzelius M, Ljungqvist M, Bottai M , et al. F11 is associated with recurrent VTE in women. A prospective cohort study. Thromb Haemost 2016; 115 (2) 406-414
    Article in Thieme ConnectPubMedGoogle Scholar
  • 89 Segal JB, Brotman DJ, Necochea AJ , et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA 2009; 301 (23) 2472-2485
    CrossrefPubMedGoogle Scholar
  • 90 Lijfering WM, Middeldorp S, Veeger NJ , et al. Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A. Circulation 2010; 121 (15) 1706-1712
    CrossrefPubMedGoogle Scholar
  • 91 Dahlbäck B. Blood coagulation. Lancet 2000; 355 (9215) 1627-1632
    CrossrefPubMedGoogle Scholar
  • 92 Wichers IM, Tanck MW, Meijers JC , et al. Assessment of coagulation and fibrinolysis in families with unexplained thrombophilia. Thromb Haemost 2009; 101 (3) 465-470
    PubMedGoogle Scholar
  • 93 Schambeck CM, Hinney K, Haubitz I, Mansouri Taleghani B, Wahler D, Keller F. Familial clustering of high factor VIII levels in patients with venous thromboembolism. Arterioscler Thromb Vasc Biol 2001; 21 (2) 289-292
    CrossrefPubMedGoogle Scholar
  • 94 Cleuren AC, van Vlijmen BJ, Reitsma PH. Transgenic mouse models of venous thrombosis: fulfilling the expectations?. Semin Thromb Hemost 2007; 33 (6) 610-616
    Article in Thieme ConnectPubMedGoogle Scholar
  • 95 Manolio TA, Collins FS, Cox NJ , et al. Finding the missing heritability of complex diseases. Nature 2009; 461 (7265) 747-753
    CrossrefPubMedGoogle Scholar
  • 96 Zöller B, Ji J, Sundquist J, Sundquist K. Family history and risk of hospital treatment for varicose veins in Sweden. Br J Surg 2012; 99 (7) 948-953
    CrossrefPubMedGoogle Scholar
  • 97 Zöller B, Li X, Sundquist J, Sundquist K. Multiplex sibling history of coronary heart disease is a strong risk factor for coronary heart disease. Eur Heart J 2012; 33 (22) 2849-2855
    CrossrefPubMedGoogle Scholar
  • 98 Sundquist K, Li X. Differences in maternal and paternal transmission of coronary heart disease. Am J Prev Med 2006; 30 (6) 480-486
    CrossrefPubMedGoogle Scholar
  • 99 Westerdahl C, Li X, Sundquist J, Sundquist K, Zöller B. Family history as a predictor of hospitalization for hypertension in Sweden. J Hypertens 2013; 31 (10) 1952-1958
    CrossrefPubMedGoogle Scholar
  • 100 Zöller B, Ohlsson H, Sundquist J, Sundquist K. High familial risk of atrial fibrillation/atrial flutter in multiplex families: a nationwide family study in Sweden. J Am Heart Assoc 2013; 2 (1) e003384
    PubMedGoogle Scholar
  • 101 Hemminki K, Li X, Sundquist K, Sundquist J. Familial risks for type 2 diabetes in Sweden. Diabetes Care 2010; 33 (2) 293-297
    CrossrefPubMedGoogle Scholar
  • 102 Akrawi DS, Li X, Sundquist J, Fjellstedt E, Sundquist K, Zöller B. Familial risks of glomerulonephritis - a nationwide family study in Sweden. Ann Med 2016; 48 (5) 313-322
    CrossrefPubMedGoogle Scholar
  • 103 Brandt A, Bermejo JL, Sundquist J, Hemminki K. Familial risks of breast and prostate cancers: does the definition of the at risk period matter?. Eur J Cancer 2010; 46 (4) 752-757
    CrossrefPubMedGoogle Scholar
  • 104 Grimm T, Zerres K. Genetic counseling and prenatal diagnosis. In: Speicher M, Antonarakis SE, Motulsky AG, eds. Vogel and Motulsky's Human Genetics: Problems and Approaches. 4th ed. Berlin Heidelberg: Springer-Verlag; 2010: 845-866
    CrossrefGoogle Scholar
  • 105 Carter CO, Evans KA. Inheritance of congenital pyloric stenosis. J Med Genet 1969; 6 (3) 233-254
    CrossrefPubMedGoogle Scholar
  • 106 Andersson T, Alfredsson L, Källberg H, Zdravkovic S, Ahlbom A. Calculating measures of biological interaction. Eur J Epidemiol 2005; 20 (7) 575-579
    CrossrefPubMedGoogle Scholar
  • 107 Greenland S, Lash TL, Rothman KJ. Concepts of interaction. In: Rothman KJ, Greenland S, Lash TL, eds. Modern Epidemiology. Philadelphia, PA: Lippincott Williams & Wilkins; 2008: 71-83
    Google Scholar
  • 108 Zöller B, Palmer K, Li X, Sundquist J, Sundquist K. Family history of venous thromboembolism and risk of hospitalized thromboembolism in cancer patients: A nationwide family study. Thromb Res 2015; 136 (3) 573-581
    CrossrefPubMedGoogle Scholar
  • 109 Zöller B, Ohlsson H, Sundquist J, Sundquist K. Family history of venous thromboembolism is a risk factor for venous thromboembolism in combined oral contraceptive users: a nationwide case-control study. Thromb J 2015; 13: 34
    CrossrefPubMedGoogle Scholar
  • 110 Guttmacher AE, Collins FS, Carmona RH. The family history—more important than ever. N Engl J Med 2004; 351 (22) 2333-2336
    CrossrefPubMedGoogle Scholar
  • 111 Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28 (3) 370-372
    CrossrefPubMedGoogle Scholar