# Analysis of Whole Genome Sequence and Hemostasis Phenotypes

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $711,387

## Abstract

PROJECT SUMMARY
 Fibrinogen, coagulation factor VII (FVII) and factor VIII (FVIII), and its carrier protein von Willebrand factor
(vWF) play key roles in modulating the risk of arterial and venous thrombosis. Similarly, D-dimer and tissue
plasminogen activator (tPA) reflect ongoing activation of the hemostatic system, and plasminogen activator
inhibitor (PAI-1) is the principal inhibitor of tPA. These 7 factors reflect the primary hemostasis phenotypes that
have been most commonly measured in population-based studies of healthy adults. Genome-wide association
studies (GWAS) successfully identified 70 loci contributing to these clinically relevant phenotypes related to
thrombosis and hemostasis. The availability of whole genome sequencing (WGS) data in many of the studies
that contributed to these initial efforts will now allow us to expand our knowledge of the genetic variation
contributing to plasma levels of these hemostasis traits. The goal of the proposed research is to utilize existing
WGS-related resources in multi-ethnic studies to facilitate new genomic discovery in clinically-relevant
phenotypes related to thrombosis and hemostasis.
 We build upon a long-standing history of active collaboration and productivity, and have assembled the
largest collection of studies with WGS data (n=37,036 individuals) and measurements for the 7 hemostasis
phenotypes (fibrinogen, FVII, FVIII, vWF, D-dimer, tPa, and PAI-1). Generation of WGS data has been
supported by NIH initiatives such as the Cohorts for Heart and Aging Research in Genomic Epidemiology
(CHARGE) Consortium, the Trans-Omics for Precision Medicine (TOPMed) Program, the Centers for Common
Disease Genomics (CCDG), and others. This project provides a coordinated approach for detailed
interrogation of genomic data by, (1) utilizing WGS from 10 multi-ethnic studies to assess the contribution of
low frequency and rare genetic variation to 7 hemostasis phenotypes; (2) replicating significant findings in
>135,000 individuals from an additional 26 studies with imputed genotypes based on TOPMed as a reference
panel; and (3) integrating gene expression measurements with summary association statistics from a large-
scale common variant GWAS for hemostasis traits involving all 36 studies, then using WGS to interrogate
newly discovered genes. These approaches will identify genetic variation contributing to hemostasis traits that
will then be evaluated for association with clinical outcomes (e.g., venous thromboembolism, myocardial
infarction, and stroke).
 This proposal brings together extensive WGS resources, hemostasis phenotypes, and capitalizes on
advances in genomic technologies and computational analysis in order to contribute to the evidence base that
may be used to deliver precision medicine in clinical settings.

## Key facts

- **NIH application ID:** 9886277
- **Project number:** 5R01HL139553-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Alanna C Morrison
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $711,387
- **Award type:** 5
- **Project period:** 2018-02-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886277

## Citation

> US National Institutes of Health, RePORTER application 9886277, Analysis of Whole Genome Sequence and Hemostasis Phenotypes (5R01HL139553-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9886277. Licensed CC0.

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