TY - JOUR
T1 - Genetic Risk Score for Intracranial Aneurysms
T2 - Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity
AU - CADISP group
AU - International Consortium for Blood Pressure, International Headache Genetics Consortium
AU - International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group
AU - Bakker, Mark K.
AU - Kanning, Jos P.
AU - Abraham, Gad
AU - Martinsen, Amy E.
AU - Winsvold, Bendik S.
AU - Zwart, John Anker
AU - Bourcier, Romain
AU - Sawada, Tomonobu
AU - Koido, Masaru
AU - Kamatani, Yoichiro
AU - Morel, Sandrine
AU - Amouyel, Philippe
AU - Debette, Stéphanie
AU - Bijlenga, Philippe
AU - Berrandou, Takiy
AU - Ganesh, Santhi K.
AU - Bouatia-Naji, Nabila
AU - Jones, Gregory
AU - Bown, Matthew
AU - Rinkel, Gabriel J.E.
AU - Veldink, Jan H.
AU - Ruigrok, Ynte M.
AU - Hege Aamodt, Anne
AU - Heidi Skogholt, Anne
AU - Brumpton, Ben M.
AU - Willer, Cristen J.
AU - Sandset, Else C.
AU - Kristoffersen, Espen S.
AU - Ellekjær, Hanne
AU - Heuch, Ingrid
AU - Nielsen, Jonas B.
AU - Hagen, Knut
AU - Hveem, Kristian
AU - Fritsche, Lars G.
AU - Thomas, Laurent F.
AU - Pedersen, Linda M.
AU - Gabrielsen, Maiken E.
AU - Holmen, Oddgeir L.
AU - Børte, Sigrid
AU - Zhou, Wei
AU - Abboud, Shérine
AU - Pandolfo, Massimo
AU - Thijs, Vincent
AU - Leys, Didier
AU - Bodenant, Marie
AU - Louillet, Fabien
AU - Touzé, Emmanuel
AU - Mas, Jean Louis
AU - Samson, Yves
AU - Hottenga, Jouke Jan
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/3
Y1 - 2023/3
N2 - 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=-4.82×10-3per year [95% CI, -6.49×10-3to -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.
AB - 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=-4.82×10-3per year [95% CI, -6.49×10-3to -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.
KW - Aneurysmal subarachnoid hemorrhage
KW - Genetic heterogeneity
KW - Genetics
KW - Intracranial aneurysm
KW - Risk assessment
UR - https://www.scopus.com/pages/publications/85149053073
U2 - 10.1161/STROKEAHA.122.040715
DO - 10.1161/STROKEAHA.122.040715
M3 - Article
C2 - 36655558
AN - SCOPUS:85149053073
SN - 0039-2499
VL - 54
SP - 810
EP - 818
JO - Stroke
JF - Stroke
IS - 3
ER -