Journal Article

DZNE-2021-00136

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.

Bakker, M. K. ; van der Spek, R. A. 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. M. ; 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. M. ; Friedrich, C. M. ; Hirsch, S. ; Schilling, S. ; Dauvillier, J. ; Martin, O. ; Stroke, H. A. (Collaboration Author) ; Group, C. K. B. C. (Collaboration Author) ; Consortium, B. J. P. (Collaboration Author) ; Group, I. S. (Collaboration Author) ; Group, C. (Collaboration Author) ; Genetics ; Haemorrhage, O. S. (Collaboration Author) ; Consortium, I. S. G. (Collaboration Author) ; Jones, G. T. ; Bown, M. J. ; Ko, N. U. ; Kim, H. ; Coleman, J. R. I. ; Breen, G. ; Zaroff, J. G. ; Klijn, C. J. M. ; Malik, R. ; Dichgans, M.DZNE* ; Sargurupremraj, M. ; Tatlisumak, T. ; Amouyel, P. ; Debette, S. ; Rinkel, G. J. E. ; 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. ; Bian, Z. ; Chen, J. ; Chen, Y. ; Clarke, R. ; Collins, R. ; Guo, Y. ; Han, X. ; Hill, M. ; Liu, D. ; Lv, J. ; Millwood, I. ; Peto, R. ; Sansome, S. ; Walters, R. ; Yang, X. ; Yu, C. ; Bonner, S. ; Walsh, D. ; Bulters, D. ; Kitchen, N. ; Brown, M. ; Grieve, J. ; Dichgans, M.

2020
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-020-00725-7

Abstract: Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Keyword(s): Asian People: genetics (MeSH) ; Asian Continental Ancestry Group: genetics (MeSH) ; Blood Pressure: genetics (MeSH) ; Case-Control Studies (MeSH) ; Endothelial Cells: pathology (MeSH) ; European Continental Ancestry Group: genetics (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Genome-Wide Association Study (MeSH) ; Humans (MeSH) ; Hypertension: genetics (MeSH) ; Hypertension: physiopathology (MeSH) ; Intracranial Aneurysm: genetics (MeSH) ; Intracranial Aneurysm: pathology (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Risk Factors (MeSH) ; Smoking: adverse effects (MeSH) ; Smoking: genetics (MeSH) ; Subarachnoid Hemorrhage: genetics (MeSH) ; Subarachnoid Hemorrhage: pathology (MeSH) ; White People: genetics (MeSH)

Note: ISSN 1546-1718 not unique: **3 hits**.

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Bakker, M. K. ; van der Spek, R. A. A. ; van Rheenen, W. ; et al
Author Correction: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
Nature genetics 53(2), 254 - 254 (2021) [10.1038/s41588-020-00760-4]2021   Files BibTeX | EndNote: XML, Text | RIS

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