|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
Hostettler, Isabel C.
Alg, Varinder S.
van Eijk, Kristel R.
Walters, Robin G.
Millwood, Iona Y.
Rouleau, Guy A.
Sudlow, Cathie L. M.
van den Berg, Leonard H.
Winsvold, Bendik S.
Johnsen, Marianne Bakke
Brumpton, Ben M.
Sandvei, Marie Søfteland
Willer, Cristen J.
Verschuren, W. M. Monique
Friedrich, Christoph M.
Jones, Gregory T.
Bown, Matthew J.
Ko, Nerissa U.
Coleman, Jonathan R. I.
Zaroff, Jonathan G.
Klijn, Catharina J. M.
Rinkel, Gabriel J. E.
Worrall, Bradford B.
Gaál-Paavola, Emília I.
Jääskeläinen, Juha E.
von Und Zu Fraunberg, Mikael
Broderick, Joseph P.
Werring, David J.
Veldink, Jan H.
Ruigrok, Ynte M.
|Published in:||Nature Genetics|
|Publisher / Ed. Institution:||Nature Publishing Group|
|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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