Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity. Issue 3 (19th January 2023)

• Record Type: Journal Article
• Authors: Bakker, Mark K.; Kanning, Jos P.; Abraham, Gad; Martinsen, Amy E.; Winsvold, Bendik S.; Zwart, John-Anker; Bourcier, Romain; Sawada, Tomonobu; Koido, Masaru; Kamatani, Yoichiro; Morel, Sandrine; Amouyel, Philippe; Debette, Stéphanie; Bijlenga, Philippe; Berrandou, Takiy; Ganesh, Santhi K.; Bouatia-Naji, Nabila; Jones, Gregory; Bown, Matthew; Rinkel, Gabriel J.E.; Veldink, Jan H.; Ruigrok, Ynte M.
• Other Names: Hege Aamodt Anne author non-byline.; Heidi Skogholt Anne author non-byline.; Brumpton Ben M author non-byline.; Willer Cristen J author non-byline.; Sandset Else C author non-byline.; Kristoffersen Espen S author non-byline.; Ellekjær Hanne author non-byline.; Heuch Ingrid author non-byline.; Nielsen Jonas B author non-byline.; Hagen Knut author non-byline.; Hveem Kristian author non-byline.; Fritsche Lars G author non-byline.; Thomas Laurent F author non-byline.; Pedersen Linda M author non-byline.; Gabrielsen Maiken E author non-byline.; Holmen Oddgeir L author non-byline.; Børte Sigrid author non-byline.; Zhou Wei author non-byline.; Abboud Shérine author non-byline.; Pandolfo Massimo author non-byline.; Thijs Vincent author non-byline.; Leys Didier author non-byline.; Bodenant Marie author non-byline.; Louillet Fabien author non-byline.; Touzé Emmanuel author non-byline.; Mas Jean-Louis author non-byline.; Samson Yves author non-byline.; Leder Sara author non-byline.; 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M. Monique author non-byline.; Walters Robin G. author non-byline.; Werring David J. author non-byline.; Willer Cristen J. author non-byline.; Woo Daniel author non-byline.; Worrall Bradford B. author non-byline.; Zhou Sirui author non-byline.;
• Is Part Of: Stroke. Volume 54:Issue 3(2023)
• Page Start: 810
• Page End: 818
• Publication Date: 2023-01-19
• Subjects: aneurysmal subarachnoid hemorrhage -- genetic heterogeneity -- genetics -- intracranial aneurysm -- risk assessment; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.122.040715
• Languages: English
• ISSNs: 0039-2499

Abstract

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.