# Genetics of Early-Onset Ischemic Stroke Consortium

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $583,407

## Abstract

Ischemic stroke is the 4th leading cause of death in the U.S. and a major cause of disability. The etiology of
stroke is multifactorial and poorly understood. Genetics is a potentially powerful tool for better understanding
disease etiology as it can highlight biological mechanisms underlying disease and point the way to improved
prevention and treatment. Efforts to decipher the genetic underpinnings of ischemic stroke have been
hampered because of its heterogeneity. Our study addresses this problem by focusing on early-onset
ischemic stroke (i.e., onset < 60 years), a particularly devastating manifestation of stroke because of its toll on
child rearing and the ability to work. Early-onset ischemic stroke comprises ~ 20% of all first-ever stroke and
this proportion is increasing. Studying early onset forms of other common genetic diseases (e.g., cancers,
heart disease, diabetes) has provided valuable insights about disease etiology because of the enrichment of
genetic causes. Our overall hypothesis is that early-onset ischemic stroke is enriched for genetic signals that
may highlight biological mechanisms underlying stroke and point the way to improved prevention and
treatment strategies. While the potential utility in studying early-onset ischemic stroke has been well
recognized, a major limitation has been the accrual of large sample sizes. We have taken a large step to
overcome the primary limitation of insufficient sample size by pulling together a multicenter early-onset stroke
genetics consortium that includes up to 13,500 cases already genotyped for common and rare variants, the
latter allowing us to test compelling hypotheses assessing the contribution of low frequency variants to early-
onset stroke susceptibility.
 The primary goals of our study are to detect common and rare variants associated with early-onset
ischemic stroke through genome-wide association analysis of GWAS and exome arrays in up to 13,500 early-
onset ischemic stroke cases and 94,000 controls from 16 participating cohorts. For the newly discovered
stroke-associated loci, we will identify causal variants, genes, and pathways using multiple bioinformatics
approaches. We will also determine if the newly discovered stroke-associated loci are also associated with
older onset stroke and with serum levels of biomarkers reflective of prothrombotic activity. Finally, we will test
for shared genetic risk between early-onset IS and deep venous thrombosis using polygenic risk scores and
LD regression.
 The successful identification of novel pathways and drug targets has the potential to transform our
understanding of the stroke pathophysiology and lead to more effective preventive strategies. Our study will
leverage the advantages of early-onset IS cases for genetic studies, and will also be the most well-powered
examination to date of the role of rare variants in early onset IS etiology. The proposed study will establish a
unique resource for continued studies of the genetic bas...

## Key facts

- **NIH application ID:** 9830693
- **Project number:** 5R01NS105150-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** STEVEN J KITTNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $583,407
- **Award type:** 5
- **Project period:** 2018-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830693

## Citation

> US National Institutes of Health, RePORTER application 9830693, Genetics of Early-Onset Ischemic Stroke Consortium (5R01NS105150-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830693. Licensed CC0.

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