TY - JOUR
T1 - Epidemiology of Familial Aggregation of Venous Thromboembolism
AU - Zöller, Bengt
AU - Li, Xinjun
AU - Ohlsson, Henrik
AU - Ji, Jianguang
AU - Memon, Ashfaque A.
AU - Svensson, Peter J.
AU - Palmér, Karolina
AU - Dahlbäck, Björn
AU - Sundquist, Jan
AU - Sundquist, Kristina
N1 - Publisher Copyright:
© Thieme Medical Publishers333 Seventh Avenue, New York, NY 10001, USA.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - epidemiology
KW - genetics
KW - thrombophilia
KW - venous thromboembolism
KW - venous thrombosis
UR - http://www.scopus.com/inward/record.url?scp=84992166177&partnerID=8YFLogxK
U2 - 10.1055/s-0036-1593543
DO - 10.1055/s-0036-1593543
M3 - Article
C2 - 27764883
AN - SCOPUS:84992166177
SN - 0094-6176
VL - 42
SP - 821
EP - 832
JO - Seminars in Thrombosis and Hemostasis
JF - Seminars in Thrombosis and Hemostasis
IS - 8
ER -