Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity

Research output: Contribution to journalArticle

Standard

Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity. / Olsson, M.; Stanne, T. M.; Pedersen, A.; Lorentzen, E.; Kara, E.; Martinez-Palacian, A.; Rønnow Sand, N. P.; Jacobsen, A. F.; Sandset, P. M.; Sidelmann, J. J.; Engström, G.; Melander, O.; Kanse, S. M.; Jern, C.

In: Journal of Thrombosis and Haemostasis, Vol. 16, No. 10, 2018, p. 2024-2034.

Research output: Contribution to journalArticle

Harvard

Olsson, M, Stanne, TM, Pedersen, A, Lorentzen, E, Kara, E, Martinez-Palacian, A, Rønnow Sand, NP, Jacobsen, AF, Sandset, PM, Sidelmann, JJ, Engström, G, Melander, O, Kanse, SM & Jern, C 2018, 'Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity', Journal of Thrombosis and Haemostasis, vol. 16, no. 10, pp. 2024-2034. https://doi.org/10.1111/jth.14258

APA

Olsson, M., Stanne, T. M., Pedersen, A., Lorentzen, E., Kara, E., Martinez-Palacian, A., ... Jern, C. (2018). Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity. Journal of Thrombosis and Haemostasis, 16(10), 2024-2034. https://doi.org/10.1111/jth.14258

CBE

Olsson M, Stanne TM, Pedersen A, Lorentzen E, Kara E, Martinez-Palacian A, Rønnow Sand NP, Jacobsen AF, Sandset PM, Sidelmann JJ, Engström G, Melander O, Kanse SM, Jern C. 2018. Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity. Journal of Thrombosis and Haemostasis. 16(10):2024-2034. https://doi.org/10.1111/jth.14258

MLA

Vancouver

Author

Olsson, M. ; Stanne, T. M. ; Pedersen, A. ; Lorentzen, E. ; Kara, E. ; Martinez-Palacian, A. ; Rønnow Sand, N. P. ; Jacobsen, A. F. ; Sandset, P. M. ; Sidelmann, J. J. ; Engström, G. ; Melander, O. ; Kanse, S. M. ; Jern, C. / Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity. In: Journal of Thrombosis and Haemostasis. 2018 ; Vol. 16, No. 10. pp. 2024-2034.

RIS

TY - JOUR

T1 - Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity

AU - Olsson, M.

AU - Stanne, T. M.

AU - Pedersen, A.

AU - Lorentzen, E.

AU - Kara, E.

AU - Martinez-Palacian, A.

AU - Rønnow Sand, N. P.

AU - Jacobsen, A. F.

AU - Sandset, P. M.

AU - Sidelmann, J. J.

AU - Engström, G.

AU - Melander, O.

AU - Kanse, S. M.

AU - Jern, C.

PY - 2018

Y1 - 2018

N2 - Essentials Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited. We performed a genome-wide analysis of variants influencing FSAP activity in Scandinavian cohorts. We replicated an association for Marburg-1 and identified an association for a HABP2 stop variant. We identified a novel locus near ADCY2 as a potential additional regulator of FSAP activity. Summary: Background Factor VII-activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low-frequency missense variant Marburg-I (rs7080536) in the FSAP-encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome-wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene-based tests. Using GWAS, we confirmed the strong association between the Marburg-I variant and FSAP activity. HABP2 was also significant in the gene-based analysis, and remained significant after exclusion of Marburg-I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg-I carriers, and this finding was replicated. A secondary genome-wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg-I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity.

AB - Essentials Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited. We performed a genome-wide analysis of variants influencing FSAP activity in Scandinavian cohorts. We replicated an association for Marburg-1 and identified an association for a HABP2 stop variant. We identified a novel locus near ADCY2 as a potential additional regulator of FSAP activity. Summary: Background Factor VII-activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low-frequency missense variant Marburg-I (rs7080536) in the FSAP-encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome-wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene-based tests. Using GWAS, we confirmed the strong association between the Marburg-I variant and FSAP activity. HABP2 was also significant in the gene-based analysis, and remained significant after exclusion of Marburg-I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg-I carriers, and this finding was replicated. A secondary genome-wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg-I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity.

KW - blood coagulation factors

KW - epidemiology

KW - genetic variation

KW - hemostasis

KW - plasma

U2 - 10.1111/jth.14258

DO - 10.1111/jth.14258

M3 - Article

VL - 16

SP - 2024

EP - 2034

JO - Journal of Thrombosis and Haemostasis

T2 - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 10

ER -