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

Gaunt T.R., Zabaneh D., Shah S., Guyatt A., Ladroue C., Kumari M., Drenos F., Shah T., Talmud P.J., Casas J.P., Lowe G., Rumley A., Lawlor D.A., Kivimaki M., Whittaker J., Hingorani A.D., Humphries S.E. and Day I.N. (2013) Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip. Thrombosis and Haemostasis, 110 5: 995-1003. doi:10.1160/TH13-02-0087


Author Gaunt T.R.
Zabaneh D.
Shah S.
Guyatt A.
Ladroue C.
Kumari M.
Drenos F.
Shah T.
Talmud P.J.
Casas J.P.
Lowe G.
Rumley A.
Lawlor D.A.
Kivimaki M.
Whittaker J.
Hingorani A.D.
Humphries S.E.
Day I.N.
Title Gene-centric association signals for haemostasis and thrombosis traits identified with the HumanCVD BeadChip
Journal name Thrombosis and Haemostasis   Check publisher's open access policy
ISSN 0340-6245
Publication date 2013-11-01
Year available 2013
Sub-type Article (original research)
DOI 10.1160/TH13-02-0087
Open Access Status Not Open Access
Volume 110
Issue 5
Start page 995
End page 1003
Total pages 9
Place of publication Stuttgart, Germany
Publisher Schattauer GmbH
Language eng
Subject 2720 Hematology
Formatted abstract
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=1.30×10-6), GCKR (rs1260326, p=1.63×10-6), ZNF259-APOA5 (rs651821, p=7.17 × 10-6) with plasma viscosity; and at CSF1 (rs333948, p=8.88×10-6) with platelet count. A pleiotropic effect was identified in GCKR which associated with factor VII (p=2.16 × 10-7) and plasma viscosity (p=1.63× 10-6), and, to a lesser extent, ZNF259-APOA5 which also associated with factor VII and fibrinogen (p<1.00 × 10-2) and plasma viscosity (p<1.00 × 10-5). Triglyceride associated variants were overrepresented in factor VII and plasma viscosity associations. Adjusting for triglyceride levels resulted in attenuation of associations at the GCKR and ZNF259-APOA5 loci. In addition to confirming previously reported associations, we identified four single nucleotide polymorphisms (SNPs) associated with plasma viscosity and platelet count and found evidence of pleiotropic effects with SNPs in GCKR and ZNF259-APOA5. These triglyceride-associated, pleiotropic SNPs suggest a possible causal role for triglycerides in coagulation.
Keyword Clotting factors
Genetic association
Haemostasis
HumanCVD
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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