Genetic risk score for intracranial aneurysms: prediction of subarachnoid hemorrhage and role in clinical heterogeneity

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  • dc.contributor.author Bakker, Mark K.
  • dc.contributor.author International Consortium for Blood Pressure
  • dc.contributor.author Intracranial Aneurysm Working Group
  • dc.date.accessioned 2024-11-08T08:20:52Z
  • dc.date.available 2024-11-08T08:20:52Z
  • dc.date.issued 2023
  • dc.description.abstract Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3 per year [95% CI, -6.49×10-3 to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
  • dc.description.sponsorship We acknowledge the support from the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation (CVON2015-08 ERASE), and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 852173). The project was funded in part by NIH grant R35HL161016 and University of Michigan Taubman Institute.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Bakker MK, Kanning JP, Abraham G, Martinsen AE, Winsvold BS, Zwart JA, et al. Genetic risk score for intracranial aneurysms: Prediction of subarachnoid hemorrhage and role in clinical heterogeneity. Stroke. 2023 Mar;54(3):810-8. DOI: 10.1161/STROKEAHA.122.040715
  • dc.identifier.doi http://dx.doi.org/10.1161/STROKEAHA.122.040715
  • dc.identifier.issn 0039-2499
  • dc.identifier.uri http://hdl.handle.net/10230/68467
  • dc.language.iso eng
  • dc.publisher American Hearth Association
  • dc.relation.ispartof Stroke. 2023 Mar;54(3):810-8
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/852173
  • dc.rights © 2023 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Aneurysmal subarachnoid hemorrhage
  • dc.subject.keyword Genetic heterogeneity
  • dc.subject.keyword Genetics
  • dc.subject.keyword Intracranial aneurysm
  • dc.subject.keyword Risk assessment
  • dc.title Genetic risk score for intracranial aneurysms: prediction of subarachnoid hemorrhage and role in clinical heterogeneity
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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