Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
Authors: Bakker, Mark K.
van der Spek, Rick A. A.
van Rheenen, Wouter
Morel, Sandrine
Bourcier, Romain
Hostettler, Isabel C.
Alg, Varinder S.
van Eijk, Kristel R.
Koido, Masaru
Akiyama, Masato
Terao, Chikashi
Matsuda, Koichi
Walters, Robin G.
Lin, Kuang
Li, Liming
Millwood, Iona Y.
Chen, Zhengming
Rouleau, Guy A.
Zhou, Sirui
Rannikmäe, Kristiina
Sudlow, Cathie L. M.
Houlden, Henry
van den Berg, Leonard H.
Dina, Christian
Naggara, Olivier
Gentric, Jean-Christophe
Shotar, Eimad
Eugène, François
Desal, Hubert
Winsvold, Bendik S.
Børte, Sigrid
Johnsen, Marianne Bakke
Brumpton, Ben M.
Sandvei, Marie Søfteland
Willer, Cristen J.
Hveem, Kristian
Zwart, John-Anker
Verschuren, W. M. Monique
Friedrich, Christoph M.
Hirsch, Sven
Schilling, Sabine
Dauvillier, Jérôme
Martin, Olivier
Jones, Gregory T.
Bown, Matthew J.
Ko, Nerissa U.
Kim, Helen
Coleman, Jonathan R. I.
Breen, Gerome
Zaroff, Jonathan G.
Klijn, Catharina J. M.
Malik, Rainer
Dichgans, Martin
Sargurupremraj, Muralidharan
Tatlisumak, Turgut
Amouyel, Philippe
Debette, Stéphanie
Rinkel, Gabriel J. E.
Worrall, Bradford B.
Pera, Joanna
Slowik, Agnieszka
Gaál-Paavola, Emília I.
Niemelä, Mika
Jääskeläinen, Juha E.
von Und Zu Fraunberg, Mikael
Lindgren, Antti
Broderick, Joseph P.
Werring, David J.
Woo, Daniel
Redon, Richard
Bijlenga, Philippe
Kamatani, Yoichiro
Veldink, Jan H.
Ruigrok, Ynte M.
et. al: No
DOI: 10.1038/s41588-020-00725-7
Published in: Nature Genetics
Volume(Issue): 52
Issue: 12
Page(s): 1303
Pages to: 1313
Issue Date: 16-Nov-2020
Publisher / Ed. Institution: Nature Publishing Group
ISSN: 1061-4036
Language: English
Subjects: Cerebrovascular disorder; Genome-wide association study; Stroke; Intracranial aneurysm; Genetic risk factor
Subject (DDC): 572: Biochemistry
616: Internal medicine and diseases
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.
Fulltext version: Published version
License (according to publishing contract): Licence according to publishing contract
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Computational Life Sciences (ICLS)
Published as part of the ZHAW project: AneuX
Appears in collections:Publikationen Life Sciences und Facility Management

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