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Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.

Publication ,  Journal Article
Bakker, MK; Kanning, JP; Abraham, G; Martinsen, AE; Winsvold, BS; Zwart, J-A; Bourcier, R; Sawada, T; Koido, M; Kamatani, Y; Morel, S; Bown, M ...
Published in: Stroke
March 2023

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.

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Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

March 2023

Volume

54

Issue

3

Start / End Page

810 / 818

Location

United States

Related Subject Headings

  • Subarachnoid Hemorrhage
  • Smoking
  • Risk Factors
  • Neurology & Neurosurgery
  • Intracranial Aneurysm
  • Incidence
  • Humans
  • 4201 Allied health and rehabilitation science
  • 3209 Neurosciences
  • 3202 Clinical sciences
 

Citation

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Bakker, M. K., Kanning, J. P., Abraham, G., Martinsen, A. E., Winsvold, B. S., Zwart, J.-A., … HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, . (2023). Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity. Stroke, 54(3), 810–818. https://doi.org/10.1161/STROKEAHA.122.040715
Bakker, Mark K., Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, et al. “Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.Stroke 54, no. 3 (March 2023): 810–18. https://doi.org/10.1161/STROKEAHA.122.040715.
Bakker MK, Kanning JP, Abraham G, Martinsen AE, Winsvold BS, Zwart J-A, et al. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity. Stroke. 2023 Mar;54(3):810–8.
Bakker, Mark K., et al. “Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.Stroke, vol. 54, no. 3, Mar. 2023, pp. 810–18. Pubmed, doi:10.1161/STROKEAHA.122.040715.
Bakker MK, Kanning JP, Abraham G, Martinsen AE, Winsvold BS, Zwart J-A, Bourcier R, Sawada T, Koido M, Kamatani Y, Morel S, Amouyel P, Debette S, Bijlenga P, Berrandou T, Ganesh SK, Bouatia-Naji N, Jones G, Bown M, Rinkel GJE, Veldink JH, Ruigrok YM, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity. Stroke. 2023 Mar;54(3):810–818.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

March 2023

Volume

54

Issue

3

Start / End Page

810 / 818

Location

United States

Related Subject Headings

  • Subarachnoid Hemorrhage
  • Smoking
  • Risk Factors
  • Neurology & Neurosurgery
  • Intracranial Aneurysm
  • Incidence
  • Humans
  • 4201 Allied health and rehabilitation science
  • 3209 Neurosciences
  • 3202 Clinical sciences