• Femke N G van 't Hof, Mitja I Kurki, Rachel Kleinloog, Paul I W de Bakker, Mikael von und zu Fraunberg, Juha E Jääskeläinen, Emília I Gaál, Hanna Lehto, Riku Kivisaari, Aki Laakso, Mika Niemelä, Juha Hernesniemi, Matthijs C Brouwer, Diederik van de Beek, Gabriël J E Rinkel, and Ynte M Ruigrok.
• From the Utrecht Stroke Center, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience (F.N.G.v.t.H., R. Kleinloog, G.J.E.R., Y.M.R.), and Departments of Epidemiology (P.I.W.d.B.) and Medical Genetics (P.I.W.d.B.), University Medical Center Utrecht, the Netherlands; Neurosurgery of NeuroCenter (M.I.K., M.v.u.z.F., J.E.J.), Kuopio University Hospital; Public Health Genomics Unit (E.I.G., A.L.), Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki; Institute for Molecular Medicine Finland (E.I.G.), University of Helsinki; Department of Neurosurgery (E.I.G., H.L., R. Kivisaari, M.N., J.H.), Helsinki University Central Hospital, Finland; and Department of Neurology (M.C.B., D.v.d.B.), Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. f.vanthof@umcutrecht.nl.
• Neurology. 2014 Jul 1; 83 (1): 34-9.

ObjectiveWe investigated whether risk alleles of single nucleotide polymorphisms associated with intracranial aneurysm (IA) are enriched in patients with familial IA, IA located at the middle cerebral artery (MCA), or IA rupture at a younger age.MethodsIn this case-only study, we calculated genetic risk scores (GRS) for 973 Dutch and 718 Finnish patients with IA by summing effect size-weighted risk allele counts of 7 single nucleotide polymorphisms associated with IAs previously identified through genome-wide association studies. We tested the GRS for association with presence of familial IA or IA at the MCA using logistic regression, and with age at time of IA rupture using linear regression. We also calculated odds ratios with 95% confidence intervals for the proportion of patients with each characteristic in the highest compared with the lowest GRS tertile.ResultsGRS were higher in IA at the MCA in the Dutch (p = 2.5 × 10(-4)), Finnish (p = 0.039), and combined cohort (p = 4.9 × 10(-5)). GRS were not associated with familial IA in the Dutch (p = 0.34), Finnish (p = 0.45), and combined cohort (p = 0.98), or with age at time of IA rupture in the Dutch (p = 0.28), Finnish (p = 0.86), and combined cohort (p = 0.45). In the combined cohort, odds ratios were 0.89 (0.67-1.20) for familial IA, 1.03 (0.79-1.34) for lower age, and 1.54 (1.20-1.98) for MCA aneurysms.ConclusionsOur findings suggest that genetic risk factors have a larger role in the development of IA at the MCA than at other sites, and that genetic heterogeneity should be considered in future genetic studies.© 2014 American Academy of Neurology.

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