# Risk Factors for Ischemic Stroke in Women

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $753,968

## Abstract

ABSTRACT
Stroke is the third leading cause of death in women and the leading cause of disability in the US. New
proteomic techniques measure a wide profile of proteins, providing a comprehensive picture of protein
functions. Since proteins perform most biological functions, they may be leveraged as biomarkers or drug
therapy targets. Although results for proteomics and cardiovascular disease have been promising, only one
small prospective proteomics study of ischemic stroke has been conducted.
The over-arching goal of this study is to discover novel proteome-wide and multi-omic associations for
incident ischemic stroke. Building on an established record of success in this R01, we will measure 3072
proteins (Olink platform) in the Nurses’ Health Studies (NHS; 460 ischemic strokes/ 460 controls) and VITamin
D Omega3 TriAL (VITAL; 300 ischemic strokes/ 300 controls), as well as leverage separately measured data
from the Women’s Health Initiative (WHI; 214 ischemic strokes), Framingham Heart Study Offspring Cohort
(FHSOC; 103 ischemic strokes), and UK Biobank (UKB; ~450 ischemic strokes). In Aim 1, we will test
candidate protein hypotheses in 1334 strokes in meta-analyses using Olink data from the NHS, VITAL, WHI,
FHSOC and UKB. Ischemic stroke subtypes, and interactions by sex and race will be tested. In Aim 2, we will
perform robust, proteome-wide discovery in NHS and VITAL with validation of significant proteins in meta-
analyses of WHI, FHSOC, and UKB. Validated proteins will be evaluated for causal associations using
mendelian randomization (MR) analyses. Using proteomic and genetic data from UKB (53,000), we will
generate protein polygenic allele risk scores for the validated proteins and test these protein polygenetic risk
scores for ischemic stroke in MEGASTROKE and SiGN. Ischemic stroke subtypes, and interactions by sex and
race will be explored. In Aim 3, we will leverage prior measures of metabolomic profiles and extensive
biomarker and risk factor data in NHS, VITAL and WHI, using novel integrative approaches, including similarity
network fusion, to combine proteomic and metabolomic data, biomarker and risk factor data, in associations for
ischemic stroke and stroke subtypes. Findings will be compared in NHS, VITAL and WHI.
The proposed study leverages Olink proteomic data from five cohorts to identify proteins and multi-omic
signatures integral to the incidence of stroke, which can be used to improve stroke prediction and prevention
strategies and identify new drug targets for stroke prevention.

## Key facts

- **NIH application ID:** 10519722
- **Project number:** 2R01HL088521-10A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** KATHRYN M REXRODE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $753,968
- **Award type:** 2
- **Project period:** 2008-09-11 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519722

## Citation

> US National Institutes of Health, RePORTER application 10519722, Risk Factors for Ischemic Stroke in Women (2R01HL088521-10A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10519722. Licensed CC0.

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