IP: Dra. María Sabater Lleal

Resumen del proyecto: In this project, we aim to investigate the association between 9 hemostatic factors (factor VII (FVII), factor VIII (FVIII), von Willebrand factor (VWF), factor XI (FXI), fibrinogen, tissue plasminogen activator (TPA), plasminogen activator inhibitor 1 (PAI-1), antithrombin, and protein C (PC)) and abdominal aortic aneurysm (AAA) risk. We have access to summary statistics data from meta-analyses of genoma-wide asociation studies (GWAS) performed on all the previous phenotypes, of which FVII, FVIII, VWF, antithrombin, PC and AAA are cross-ancestry meta-analyses, and fibrinogen, FXI, TPA and PAI-1 are from European ancestry. To investigate the shared genetic component between the clotting factors levels and AAA risk, we will first create polygenic risk scores (PRS) for each hemostatic factor using the genetic variants identified in the GWAS meta-analyses. We will use the PRS-CSx software, which allows for genome-wide PRS generation with multi-ancestry data, to create the PRS. We will then assess the association between the obtained PRS and AAA using logistic regression, adjusting for relevant covariates (i.e., sex, age, PCs). To do this, we need DNA sequence information from individuals with AAA and individuals without AAA (controls). The genotypic information from AAA cases, will come from the Triple-A Barcelona Study (TABS) cohort, which consists of 394 patients with AAA recruited by our research group from 3 Spanish hospitals, and we need to request genotypic data for the controls. In addition, we plan to use the data from the Danish DANCAVAS cohort, which is available to us through a collaboration, as a validation cohort, which consists of 455 genotyped individuals with AAA and 7,614 genotyped controls.

Entidad financiadora: Agencia Estatal de Investigación, Ministerio de Ciencia e Innovación