Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip

Coagulation phenotypes show strong intercorrelations, affect cardiovascular disease risk and are influenced by genetic variants. The objective of this study was to search for novel genetic variants influencing the following coagulation phenotypes: factor VII levels, fibrinogen levels, plasma viscosity and platelet count. We genotyped the British Women’s Heart and Health Study (n=3,445) and the Whitehall II study (n=5,059) using the Illumina HumanCVD BeadArray to investigate genetic associations and pleiotropy. In addition to previously reported associations (SH2B3, F7/F10, PROCR, GCKR, FGA/FGB/FGG, IL5), we identified novel associations at GRK5 (rs10128498, p=1.30x10⁻⁶), GCKR (rs1260326, p=1.63x10⁻⁶), ZNF259-APOA5 (rs651821, p=7.17x10⁻⁶) with plasma viscosity; andat CSF1 (rs333948, p=8.88x10⁻⁶) with platelet count. A pleiotropic effect was identified in GCKR which associated with factor VII (p=2.16x10⁻⁷) and plasma viscosity (p=1.63x10⁻⁶), and, to a lesser extent, ZNF259-APOA5 which also associated with factor VII and fibrinogen (p