Overlap in the Genetic Architecture of Stroke Risk, Early Neurological Changes, and Cardiovascular Risk Factors
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Background and Purpose—: The genetic relationships between stroke risk, stroke severity, and early neurological changes are complex and not completely understood. Genetic studies have identified 32 all stroke risk loci. Polygenic risk scores can be used to compare the genetic architecture of related traits. In this study, we compare the genetic architecture of stroke risk, stroke severity, and early neurological changes with that of 2 stroke risk factors: type 2 diabetes mellitus (T2DM) and hypertension. Methods—: We assessed the degree of overlap in the genetic architecture of stroke risk, T2DM, hypertension, and 2 acute stroke phenotypes based on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 for no stroke symptoms to 21 to 42 for a severe stroke: baseline (within 6 hours after onset) and change in NIHSS (ΔNIHSS=NIHSS at baseline−NIHSS at 24 hours). This was done by (1) single-nucleotide polymorphism by single-nucleotide polymorphism comparison, (2) weighted polygenic risk scores with sentinel variants, and (3) whole-genome polygenic risk scores using multiple P thresholds. Results—: We found evidence of genetic architecture overlap between stroke risk and T2DM ( P =2.53×10 − 169 ), hypertension ( P =3.93×10 − 04 ), and baseline NIHSS ( P =0.03). However, there was no evidence of overlap between ΔNIHSS and stroke risk, T2DM, or hypertension. Conclusions—: The genetic architecture of stroke risk is correlated with that of T2DM, hypertension, and initial stroke severity (NIHSS within 6 hours of stroke onset). However, the genetic architecture of early neurological change after stroke (ΔNIHSS) is not correlated with that of ischemic stroke risk, T2DM, or hypertension. Thus, stroke risk and early neurological change after stroke have distinct genetic architectures.
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E-Selectin is a known stroke biomarker.
“E-Selectin is a known stroke biomarker24, and our MR plus colocalization analyses indicated that this protein is genetically associated with the disease (Tables S27, S30).”
From Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders (2021) · cites this paper as [24]
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- Authors
- Ibanez, L., Heitsch, L., Dube, U., Farias, F. H. G., Budde, J., Bergmann, K., Davenport, R., Bradley, J., Carrera, C., Kinnunen, J., Sallinen, H., Strbian, D., Slowik, A., Fernandez-Cadenas, I., Montaner, J., Lee, J.-M., Cruchaga, C., & on behalf of the International Stroke Genetics Consortium and the MEGASTROKE Consortium*
- Affiliations
- From the Department of Psychiatry (L.I., U.D., F.H.G.F., J. Budde, K.B., R.D., J. Bradley, C. Cruchaga), Washington University School of Medicine, St. Louis, MO
- Washington University in St. Louis (US)
- Vall d'Hebron Institut de Recerca (ES)
- Helsinki University Hospital (FI)
- Department of Neurology, Jagiellonian University Medical College, Kraków, Poland (A.S.)
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Barcelona, Spain (C. Carrera, I.F.-C., J.M.)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Cruchaga, Carlos
- ORCID
- Venue
- Stroke
- Published
- 2019-06
- Volume
- 50
- Issue
- 6
- Pages
- 1339-1345
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC6538457
- OpenAlex
- W2945027013
- Cited by
- 23
- References
- 37
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 4 · 2021: 7 · 2020: 6
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, other-oa)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- American Heart Association
- Foundation for Barnes-Jewish Hospital
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Fundació la Marató de TV3
- Suomen Lääketieteen Säätiö
- Ministerio de Ciencia e Innovación
- National Institutes of Health
- Instituto de Salud Carlos III
- European Regional Development Fund
- National Institute of Neurological Disorders and Stroke (R01NS085419, K23NS099487, U24NS107230)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- stroke risk, genetic architecture, polygenic risk score, type 2 diabetes, hypertension, stroke severity, NIHSS, ischemic stroke, genetic overlap, cardiovascular risk factors
- MeSH terms
- Aged, Diabetes Mellitus, Type 2, Female, Humans, Hypertension, Male, Middle Aged, Risk Factors, Multifactorial Inheritance, Stroke, Polymorphism, Single Nucleotide, Databases, Genetic
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