# Population genomic variation, functional biology, and the risk of venous thrombosis

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $708,902

## Abstract

Abstract
The promises of precision medicine leading to healthier lives, free of the burden of cardiovascular diseases,
will be hastened by creating timely, efficient, and effective scientific conduits that rapidly move newly
characterized molecular genetic information between genetic epidemiologists and functional biologists. Within
the setting of 2 international consortia on the genetics of hemostasis phenotypes and venous
thromboembolism (VTE), a network of genetic epidemiologists have successfully collaborated to identify and to
replicate novel associations of loci with VTE and thrombosis-related phenotypes, a few of which have
undergone functional testing. The goals of this project are 2-fold: (a) to coordinate and advance new genetic
discovery in the setting of the 2 international consortia on hemostasis phenotypes (Cohorts for Health and
Aging Research in Genomic Epidemiology [CHARGE] Consortium) and VTE (International Network of Venous
Thrombosis [INVENT] Consortium); and (b) to follow-up the discoveries with functional biology work conducted
by laboratory-based research using cell and animal models that will provide new biologic insights. The
CHARGE Hemostasis Working Group coordinates genomic discovery in key hemostasis-related phenotypes
from 42 studies and the INVENT consortium coordinates genomic discovery in the VTE phenotype from 12
studies. The genetic discoveries made thus far have provided new biologic insights to the regulation of key
hemostasis proteins and VTE risk in genes not previously known to be involved biologically, such as STXBP5
and TC2N, associated with von Willebrand factor and VTE, and TSPAN15 and SLC44A2, associated with
VTE. A growing limitation to our scientific productivity has been the challenge of replication: as more studies
join consortia for discovery, fewer studies are available for replication. An alternative approach, which
accelerates scientific discovery, is to move discoveries that have been prioritized by bioinformatics resources
directly to functional testing in the laboratory. Another challenge to new discovery has been the lack of analytic
tools that are practical in the consortia setting to analyze across phenotypes in discovery efforts. Recently,
however, new approaches that use genetic correlations to facilitate multi-phenotype investigations have
emerged and can now be applied using hemostasis phenotypes. In this application, we apply these new
approaches to advance genetic and functional discovery and validation efforts via 3 aims. Each aim contains
novel work to be accomplished in the proposed 4-year project leverages existing and soon-to-be released
genomic resources to achieve the overall goal of characterizing functional physiologic diversity that leads to
clinical thrombosis in humans.

## Key facts

- **NIH application ID:** 9985141
- **Project number:** 5R01HL134894-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** CHARLES J LOWENSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $708,902
- **Award type:** 5
- **Project period:** 2017-08-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985141

## Citation

> US National Institutes of Health, RePORTER application 9985141, Population genomic variation, functional biology, and the risk of venous thrombosis (5R01HL134894-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9985141. Licensed CC0.

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