Towards the genetic basis of cerebral venous thrombosis—the BEAST Consortium: a study protocol

Abstract

IntroductionCerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated.Methods and analysisTo better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case–control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease.Ethics and disseminationBEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders.

Effects of Second Language Learning on the Plastic Aging Brain: Functional Connectivity, Cognitive Decline, and Reorganization

“…Several protocols have been used with the purpose of maintaining healthy cognitive functions (Cotlarciuc et al, 2016; Brem and Sensi, 2018). In a recent study, Ware et al (Ware et al, 2017) have shown that computer-assisted learning of a second language leads to social and motivational benefits, although they did not investigate different cognitive domains.…”

Cerebral venous sinus thrombosis

“…Additional mechanical risk factors for CVST include neurosurgery, internal jugular catheterization and lumbar puncture . Regarding genetic causes, several loci on chromosome 6 (within the human histocompatibility complex) and chromosome 9 (close to the ABO gene) have been involved in the development of CVST , although these associations remain to be confirmed in large genome‐wide association studies . The association of CVST with other candidate genes, such as plasminogen activator inhibitor‐1 4G/5G polymorphism and protein Z G79A polymorphism , remains controversial.…”

Thrombin-Activatable Fibrinolysis Inhibitor Polymorphisms and Cerebral Venous Thrombosis in Mexican Mestizo Patients

“…The genetic basis of CVT is widely unknown and has gained attention as a research question because nearly 10% to 25% of cases have no identifiable risk factors. 1,6,7 Certain gene candidates have been studied as the main genetic risk predisposition for CVT; unfortunately, due to the difficulty in achieving a sufficient sample size, multiple studies have failed to show a causative association. Factor V Leyden (G1691A polymorphism), 8 prothrombin mutation (G20210A polymorphism), 8 methylene tetrahydrofolate reductase (C677T polymorphism), 9 plasminogen-activator inhibitor-1 (4G/4G polymorphism), 10 protein Z (G79A polymorphism), 11 Janus kinase-2 (V617F polymorphism), 12 and thrombin-activatable fibrinolysis inhibitor (TAFI; A505G, C1040T, and C1542G polymorphisms) 13 are a subset of the genes possibly associated with risk of CVT development.…”