Mendelian Randomization Analysis of Hemostatic Factors and Their Contribution to Peripheral Artery Disease-Brief Report
Por:
Small, AM, Huffman, JE, Klarin, D, Sabater-Lleal, M, Lynch, JA, Assimes, TL, Sun, YV, Miller, D, Freiberg, MS, Morrison, AC, Rader, DJ, Wilson, PWF, Cho, K, Tsao, PS, Chang, KM, Smith, NL, O'Donnell, CJ, de Vries, PS, Damrauer, SM, Cohorts Heart & Aging Res Genomic, VA Million Veteran Program
Publicada:
1 ene 2021
Resumen:
Background and Objective: Peripheral artery disease (PAD) is the third most common form of atherosclerotic vascular disease and is characterized by significant functional disability and increased cardiovascular mortality. Recent genetic data support a role for a procoagulation protein variant, the factor V Leiden mutation, in PAD. The role of other hemostatic factors in PAD remains unknown. We evaluated the role of hemostatic factors in PAD using Mendelian randomization.
Approach and Results: Two-sample Mendelian randomization to evaluate the roles of FVII (factor VII), FVIII (factor VIII), FXI (factor XI), VWF (von Willebrand factor), and fibrinogen in PAD was performed using summary statistics from GWAS for hemostatic factors performed within the Cohorts for Heart and Aging Research in the Genome Epidemiology Consortium and from GWAS performed for PAD within the Million Veteran Program. Genetically determined FVIII and VWF, but not FVII, FXI, or fibrinogen, were associated with PAD in Mendelian randomization experiments (FVIII: odds ratio, 1.41 [95% CI, 1.23-1.62], P=6.0x10(-7), VWF: odds ratio, 1.28 [95% CI, 1.07-1.52], P=0.0073). In single variant sensitivity analysis, the ABO locus was the strongest genetic instrument for both FVIII and VWF.
Conclusions: Our results suggest a role for hemostasis, and by extension, thrombosis in PAD. Further study is warranted to determine whether VWF and FVIII independently affect the biology of PAD.
Filiaciones:
Small, AM:
Corporal Michael J Crescenz VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA
Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA
Huffman, JE:
Massachusetts Gen Hosp, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston VA Healthcare Syst, Boston, MA 02114 USA
Klarin, D:
Massachusetts Gen Hosp, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston VA Healthcare Syst, Boston, MA 02114 USA
Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA
Harvard Med Sch, Program Med & Populat Genet, Broad Inst & Harvard, Cambridge, MA USA
Sabater-Lleal, M:
IIB Sant Pau, Res Inst Hosp Sant Pau, Genom Complex Dis, Barcelona, Spain
Karolinska Inst, Dept Med, Ctr Mol Med, Cardiovasc Med Unit, Stockholm, Sweden
Lynch, JA:
UT, Salt Lake City Hlth Care Syst, Dept Vet Affairs, Boston, MA 02125 USA
Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA USA
Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA
Assimes, TL:
VA Palo Alto Hlth Care Syst, Palo Alto, CA USA
Stanford Univ, Sch Med, Dept Med, Stanford, CA USA
Sun, YV:
Atlanta VA Hlth Care Syst, Decatur, GA USA
Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Dept Biomed Informat, Atlanta, GA USA
Miller, D:
Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA
Boston Univ, Sch Med, Boston, MA 02118 USA
Freiberg, MS:
VA Tennessee Valley Healthcare Syst, Nashville, TN USA
Vanderbilt Univ, Med Ctr, Nashville, TN USA
Morrison, AC:
Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA
Rader, DJ:
Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
Wilson, PWF:
Atlanta VA Hlth Care Syst, Decatur, GA USA
Emory Clin Cardiovasc Res Inst, Atlanta, GA USA
Cho, K:
Massachusetts Gen Hosp, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston VA Healthcare Syst, Boston, MA 02114 USA
Tsao, PS:
VA Palo Alto Hlth Care Syst, Palo Alto, CA USA
Stanford Univ, Sch Med, Dept Med, Stanford, CA USA
Chang, KM:
Corporal Michael J Crescenz VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
Smith, NL:
Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
Kaiser Permanente Washington, Kaiser Permanente Washington Res Inst, Seattle, WA USA
Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Dept Veteran Affairs, Seattle, WA USA
O'Donnell, CJ:
Massachusetts Gen Hosp, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston VA Healthcare Syst, Boston, MA 02114 USA
Brigham & Womens Hosp, Dept Med, Cardiovasc Med Div, Cambridge, MA USA
de Vries, PS:
Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA
Damrauer, SM:
Corporal Michael J Crescenz VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA
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