Genetic Correlates of Intracranial Aneurysms

We assessed correlation between intracranial aneurysms and other traits using LDHub and LD-score regression (LDSR) with LDSC. To assess genetic correlation between intracranial aneurysms and many non-stroke-related traits, we used LD Hub^{41 (link)}. This platform uses LDSR to assess genetic correlation with a large number of publicly available GWASs. For the correlation of intracranial aneurysms and other stroke subtypes, we obtained summary statistics for All Stroke (AS), Cardioembolic Stroke (CE), Any Ischemic Stroke (AnyIS), Large Artery Stroke (LAS), Small Vessel Disease (SVD)^{42 (link)}, Deep, Lobar, and combined Intracerebral Hemorrhage (ICH)^{63 (link)}, carotid- and vertebral artery dissection^{44 (link)}, Arteriovenous Malformation (AVM)^{43 (link)} and Abdominal Aortic Aneurysms (AAA)^{45 (link)}. We used LDSC to calculate genetic correlation. LD scores from European ancestry individuals from 1000G were calculated for SNPs in the HapMap 3 SNP set and used to calculate genetic correlation. Since the heritability estimate was negative for AVM, due to the small sample size, we performed a SNP lookup of the Stage 2 intracranial aneurysm loci that passed the multiple testing threshold (P<5·10^-8) from the GWAS of AVM^{43 (link)}.

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Bakker M.K., van der Spek R.A., van Rheenen W., Morel S., Bourcier R., Hostettler I.C., Alg V.S., van Eijk K.R., Koido M., Akiyama M., Terao C., Matsuda K., Walters R.G., Lin K., Li L., Millwood I.Y., Chen Z., Rouleau G.A., Zhou S., Rannikmäe K., Sudlow C.L., Houlden H., van den Berg L.H., Dina C., Naggara O., Gentric J.C., Shotar E., Eugène F., Desal H., Winsvold B.S., Børte S., Johnsen M.B., Brumpton B.M., Sandvei M.S., Willer C.J., Hveem K., Zwart J.A., Verschuren W.M., Friedrich C.M., Hirsch S., Schilling S., Dauvillier J., Martin O., Jones G.T., Bown M.J., Ko N.U., Kim H., Coleman J.R., Breen G., Zaroff J.G., Klijn C.J., Malik R., Dichgans M., Sargurupremraj M., Tatlisumak T., Amouyel P., Debette S., Rinkel G.J., Worrall B.B., Pera J., Slowik A., Gaál-Paavola E.I., Niemelä M., Jääskeläinen J.E., von Und Zu Fraunberg M., Lindgren A., Broderick J.P., Werring D.J., Woo D., Redon R., Bijlenga P., Kamatani Y., Veldink J.H, & Ruigrok Y.M. (2020). Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nature genetics, 52(12), 1303-1313.

Publication 2020

Abdominal aortic aneurysms Arteriovenous malformation Artery Cardioembolic stroke Carotid Correlation European Gwas Hapmap Intracerebral hemorrhage Intracranial aneurysm Ischemic stroke Stroke Vertebral artery Vessel disease

Corresponding Organization :

Other organizations : University Medical Center Utrecht, Utrecht University, University of Geneva, Institut du Thorax, Inserm, Nantes Université, Centre National de la Recherche Scientifique, National Hospital for Neurology and Neurosurgery, University College London, RIKEN Center for Integrative Medical Sciences, The University of Tokyo, University of Oxford, Peking University, McGill University, Montreal Neurological Institute and Hospital, Jewish General Hospital, University of Edinburgh, Université Paris Cité, Délégation Paris 5, Centre Hospitalier Régional Universitaire de Brest, Pitié-Salpêtrière Hospital, Sorbonne Université, Centre Hospitalier Universitaire de Rennes, Université de Rennes, Centre Hospitalier Universitaire de Nantes, Oslo University Hospital, Norwegian University of Science and Technology, Michigan Medicine, Dortmund University of Applied Sciences and Arts, ZHAW Zurich University of Applied Sciences, SIB Swiss Institute of Bioinformatics, University of Otago, NIHR Leicester Cardiovascular Biomedical Research Unit, National Institute for Health Research, University of Leicester, University of California, San Francisco, King's College London, Kaiser Permanente, Radboud University Nijmegen, Radboud University Medical Center, Ludwig-Maximilians-Universität München, Bordeaux Population Health, Université de Bordeaux, University of Gothenburg, Université de Lille, Institut Pasteur de Lille, University of Virginia, Jagiellonian University, University of Helsinki, Helsinki University Hospital, Kuopio University Hospital, University of Cincinnati Medical Center, University Hospital of Geneva

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Variable analysis

independent variables

Intracranial aneurysms
Other stroke subtypes (All Stroke, Cardioembolic Stroke, Any Ischemic Stroke, Large Artery Stroke, Small Vessel Disease, Deep Intracerebral Hemorrhage, Lobar Intracerebral Hemorrhage, carotid- and vertebral artery dissection, Arteriovenous Malformation, Abdominal Aortic Aneurysms)

dependent variables

Genetic correlation between intracranial aneurysms and other traits

control variables

LD scores from European ancestry individuals from 1000G calculated for SNPs in the HapMap 3 SNP set

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