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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
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Publication History

Publication Date:
20 October 2016 (online)

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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