Genetic analysis of venous thromboembolism, peripheral artery disease, and varicose veins: Analysis of GWAS, WES and WGS data and evaluation of the clinical significance of associated variants

Background: Venous thromboembolism (VTE) is the third most common cardiovascular disease and is associated with high recurrence and mortality risks.

The underlying causes are unknown in about 40% of all VTE events and a major part of the heritability of VTE is unexplained.

Peripheral artery disease (PAD) and varicose veins (VVs) are associated with VTE and a genetic link between them has been suggested.

Aim: The project aims to identify unknown genetic risk factors for VTE, PAD, and VVs in the Malmö Diet and Cancer study (MDC, 30446 individuals) using recently obtained genome wide association study (GWAS) and whole exome sequencing (WES) data. Whole genome sequencing (WGS) will also be performed in a large thrombophilic family.

The clinical significance of identified variants will be evaluated using a clinical material of 1465 consecutive VTE patients (MATS study). Work plan: Statistical and bioinformatical analysis will be performed on GWAS, WES and WGS data. In MDC 3327 individuals are affected with VTE, 1698 with PAD, and 1706 with VVs.

All identified variants will be validated in silico and compared with database information. Clinical significance will be evaluated using targeted resequencing and genotyping in MATS study. Significance: The project will lead to new knowledge about the genetics of VTE, PAD, VVs and their interrelationships.

Identification of genetic risk factors will have impact on risk assessment, prevention, and the development of new therapies.