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Generation and Applicability of Genetic Risk Scores (GRS) in Stroke

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Stroke Biomarkers

Part of the book series: Neuromethods ((NM,volume 147))

Abstract

In this chapter genetic risk scores (GRS), also called polygenic risk scores (PRS), are described as feasible biomarkers to predict stroke risk. GRS are based on genome-wide association studies (GWAs) results. Use of GWAs has allowed the discovery of multiple variants associated with stroke which has led to an increase in stroke pathophysiology knowledge. However, it would be necessary to consider the cumulative risk of all associated variants to make GWAs results applicable in clinical practice. GRS summarize information from significant genetic variants into a single score. The most frequent way for GRS construction is based on the selection of the most significant single nucleotide polymorphisms (SNPs) from the largest GWAs for a trait. Then, allele dosage for each SNP is weighted using estimated effect sizes for each variant. Next, global fit, discrimination capacity, calibration, and reclassification of GRS have to be evaluated. Furthermore, replication in independent cohorts is necessary. Stroke is a disease with complex genetic architecture. Multiple loci with small effect sizes have been found to increase stroke risk. In this case, GRS could enable the translation of genetics into clinical practice in different ways, such as stroke risk prediction or differentiation of stroke subtypes to give specific secondary prevention drugs depending on the type of ischemic stroke.

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Author information

Authors and Affiliations

  1. Stroke Pharmacogenomics and Genetics, Fundació Docència i Recerca MútuaTerrassa, Hospital Mútua de Terrassa, Barcelona, Spain

    Natalia Cullell, Jonathan González-Sánchez, Israel Fernández-Cadenas & Jerzy Krupinski

  2. Stroke Pharmacogenomics and Genetics, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Natalia Cullell, Jonathan González-Sánchez & Israel Fernández-Cadenas

  3. Department of Neurology, Hospital Universitari Mútua Terrassa, Barcelona, Spain

    Natalia Cullell, Jonathan González-Sánchez, Israel Fernández-Cadenas & Jerzy Krupinski

  4. Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain

    Natalia Cullell

  5. Centre of Bioscience, School of HealthCare Sciences, Manchester Metropolitan, Manchester, UK

    Jonathan González-Sánchez & Jerzy Krupinski

Authors
  1. Natalia Cullell
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  2. Jonathan González-Sánchez
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  3. Israel Fernández-Cadenas
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  4. Jerzy Krupinski
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Corresponding author

Correspondence to Natalia Cullell .

Editor information

Editors and Affiliations

  1. Department of Anatomy, University of Otago, Dunedin, New Zealand

    Philip V. Peplow

  2. Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Lab, Los Alamos, NM, USA

    Bridget Martinez

  3. Brain Biomarkers Research Lab, Emory Decatur Hospital, Emory Healthcare, Decatur, GA, USA

    Svetlana A. Dambinova

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Cullell, N., González-Sánchez, J., Fernández-Cadenas, I., Krupinski, J. (2020). Generation and Applicability of Genetic Risk Scores (GRS) in Stroke. In: Peplow, P.V., Martinez, B., Dambinova, S.A. (eds) Stroke Biomarkers. Neuromethods, vol 147. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9682-7_3

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  • DOI: https://doi.org/10.1007/978-1-4939-9682-7_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9681-0

  • Online ISBN: 978-1-4939-9682-7

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