A genetic basis for the interrelation of coagulation factors

Summary Background: Evidence found in the literature for a strong correlation between coagulation factors suggests that single genes might influence the plasma concentrations of multiple coagulation factors (i.e. pleiotropically acting genes). Objective: To determine whether there is a genetic basis for the correlation among coagulation factors by assessing the heritability of interrelated coagulation factors. Patients/methods: We performed principal components analysis, and subsequently variance components analysis, to estimate the heritability of principal components of coagulation factors in family members of a large French‐Canadian kindred. Results: Four clusters were identified by principal components analysis in 200 family members who did not carry the protein C 3363C mutation. Cluster 1 consisted of prothrombin, factor VII (FVII), FIX, FX and protein S; cluster 2 consisted of FV, FIX, protein C and tissue factor pathway inhibitor; cluster 3 consisted of FVIII and von Willebrand factor; and cluster 4 consisted of antithrombin, protein C and FVII. The heritability of the principal components estimated by variance components analysis was, respectively, 37%, 100%, 37%, and 37%. Conclusion: Our findings support the hypothesis that genes can influence plasma levels of interrelated coagulation factors.