We performed a Genome-Wide Association Study (GWAS) of abnormally high activity of coagulation factor (F) IX. This increased function is associated with higher risk of cardiovascular diseases including venous thromboembolism (VTE) [1]. A total of ten genomic loci were identified: AHCTF1, GCKR, KNG, HRG, HRG-AS1, F12, ABO, and F9. In particular, the missense variant in F9 is close to a cleavage site in the protein product (FIX) and could affect its processing. A polygenic score assessing the effect of mutations in the ten loci was associated with hemostatic phenotypes (activated partial thromboplastin time, FVIII, FXI, and FXII activity) and metabolic phenotypes (triglycerides, gamma-glutamyl transferase, and low-density lipoprotein cholesterol levels). Our analyses suggest detrimental effects of FIX activity on VTE.
References
[1] Han, J., V. ten Cate, R. Li-Gao, A. Pallares Robles, H. Raaja Sulochana, M.A. Andrade-Navarro, L. Ao, R. Noordam, A. Martinez-Perez, M. Sabater-Lleal, J.M. Soria, J.C. Souto, F.R. Rosendaal, P.S. Wild, A. van Hylckama Vlieg. 2025. Genome-wide identification of loci associated with plasma coagulation factor IX activity. J. Thromb. Haemost. In press.