NHLBI TOPMed: Whole Genome Sequencing of Venous Thromboembolism (WGS of VTE)

This study is part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequencing Program. TOPMed is part of a broader Precision Medicine Initiative, which aims to provide disease treatments that are tailored to an individual's unique genes and environment. TOPMed will contribute to this initiative through the integration of whole-genome sequencing (WGS) and other -omics (e.g., metabolic profiles, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data. In doing so, this program aims to uncover factors that increase or decrease the risk of disease, to identify subtypes of disease, and to develop more targeted and personalized treatments. Two genotype call sets derived from WGS are now available, Freeze 8 (GRCh38) and Freeze 9b (GRCh38), with largely overlapping sample sets. Information about how to identify other TOPMed WGS accessions for cross-study analysis, as well as descriptions of TOPMed methods of data acquisition, data processing and quality control, are provided in the accompanying documents, "TOPMed Whole Genome Sequencing Project - Freeze 8, Phases 1-4" and "TOPMed Whole Genome Sequencing Project - Freeze 9b, Phases 1-4". Please check the study list at the top of each of these methods documents to determine whether it applies to this study accession.

This study consists of 338 VTE cases from an inception cohort of Olmsted County, MN residents (OC) with a first lifetime objectively-diagnosed idiopathic VTE during the 40-year study period, 1966-2005. All living study subjects were invited to provide a whole blood sample at the Mayo Clinical Research Unit for leukocyte genomic DNA and plasma collection. For living study subjects who did not provide a blood sample, we retrieved any leftover blood ("waste" blood) from samples collected as part of routine clinical diagnostic testing and used this to extract DNA after obtaining patient consent. For deceased cases, with IRB approval, we extracted DNA from any available stored tissue within the Mayo Tissue Archive. This "tissue" DNA has been successfully genotyped in prior studies. Three trained and experienced study nurse abstractors reviewed the complete medical records in the community of all potential cases.

Note: WGS sample IDs for the previous GENEVA study cases (phs000289) are included in this dataset. The phenotypes for the GENEVA study are located under the above phs number.

• Study Design:
  • Case Set
• Study Type:
  • Case Set
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 1535
• Subject Sample Telemetry Report (SSTR)

For cases meeting our definition of an incident idiopathic deep vein thrombosis (DVT) or pulmonary embolism (PE) and our Olmsted County residency requirements, the study nurse abstractors collected information on date of incident VTE onset, VTE event type, patient age at incident VTE event date, gender, patient location at incident VTE event onset (community, hospital, or nursing home), vital status at last clinical contact, dates of initiation and completion of standard heparin, LMWH and warfarin therapy, date of first VTE recurrence and new exposures or new chronic diseases diagnosed or new anticoagulation therapy for an indication other than VTE (e.g., atrial fibrillation) in the interval between the incident and recurrent VTE.

We excluded VTE cases that were not idiopathic (for example, if they were related to pregnancy or oral contraceptive pills (women only), hospitalization, trauma, surgery, and cancer).

• Primary Phenotype: Venous Thromboembolism
• Deep Venous Thrombosis
• Pulmonary Embolism

• ABO
• F2
• F5

• BioProject
• PubMed
• Sequence Read Archive
• BioSample
• MeSH
• PMC