Next-generation DNA sequencing to identify novel genetic risk factors for cerebral vein thrombosis.
Thromb Res
; 169: 76-81, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30029070
ABSTRACT
BACKGROUND:
Cerebral vein thrombosis (CVT) is a rare, life-threatening disease affecting one adult per 100,000 per year. Genetic risk factors are deficiencies of the natural anticoagulant proteins antithrombin, protein C, protein S or single nucleotide polymorphisms such as factor V Leiden and prothrombin 20210A. In 20% of patients, the cause of CVT remains unknown.AIM:
To identify novel genetic risk factors for CVT using targeted next-generation DNA sequencing (NGS).METHODS:
We investigated 171 CVT patients and 298 healthy controls. Patients were selected using the following criteria objective diagnosis of CVT, no active cancer. We performed targeted NGS analysis of the protein-coding regions of 734 candidate genes related to hemostasis and inflammation, 150 ancestry informative markers and 28 thrombosis-associated variants.RESULTS:
We identified 3723 common and low frequency variants with minor allele frequency (MAF) >1% in 590 genes. Single variant association testing using logistic regression analysis identified rs8176719 insertion/deletion (indel) variant in the ABO gene associated with CVT (age and sex adjusted OR 2.03; 95% CI 1.52-2.73; Pâ¯=â¯2.07â¯×â¯10-6; Bonferroni Pâ¯=â¯0.008). In addition, we identified 8839 rare variants (MAFâ¯≤â¯1%) in 723 genes. Gene-based association analysis of these rare variants using a burden test revealed only a tentative association of non-coding variants located in the F8 locus with CVT.CONCLUSION:
Targeted NGS identified a common indel variant rs8176719 in the ABO gene. Gene-based tests of association failed to reveal genomic loci with a cumulative burden of rare variants associated with CVT.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Veias Cerebrais
/
Trombose Intracraniana
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Thromb Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Itália