TY  - JOUR
AU  - Bakker, Mark K
AU  - van der Spek, Rick A A
AU  - van Rheenen, Wouter
AU  - Morel, Sandrine
AU  - Bourcier, Romain
AU  - Hostettler, Isabel C
AU  - Alg, Varinder S
AU  - van Eijk, Kristel R
AU  - Koido, Masaru
AU  - Akiyama, Masato
AU  - Terao, Chikashi
AU  - Matsuda, Koichi
AU  - Walters, Robin G
AU  - Lin, Kuang
AU  - Li, Liming
AU  - Millwood, Iona Y
AU  - Chen, Zhengming
AU  - Rouleau, Guy A
AU  - Zhou, Sirui
AU  - Rannikmäe, Kristiina
AU  - Sudlow, Cathie L M
AU  - Houlden, Henry
AU  - van den Berg, Leonard H
AU  - Dina, Christian
AU  - Naggara, Olivier
AU  - Gentric, Jean-Christophe
AU  - Shotar, Eimad
AU  - Eugène, François
AU  - Desal, Hubert
AU  - Winsvold, Bendik S
AU  - Børte, Sigrid
AU  - Johnsen, Marianne Bakke
AU  - Brumpton, Ben M
AU  - Sandvei, Marie Søfteland
AU  - Willer, Cristen J
AU  - Hveem, Kristian
AU  - Zwart, John-Anker
AU  - Verschuren, W M Monique
AU  - Friedrich, Christoph M
AU  - Hirsch, Sven
AU  - Schilling, Sabine
AU  - Dauvillier, Jérôme
AU  - Martin, Olivier
AU  - Genetics
AU  - Jones, Gregory T
AU  - Bown, Matthew J
AU  - Ko, Nerissa U
AU  - Kim, Helen
AU  - Coleman, Jonathan R I
AU  - Breen, Gerome
AU  - Zaroff, Jonathan G
AU  - Klijn, Catharina J M
AU  - Malik, Rainer
AU  - Dichgans, Martin
AU  - Sargurupremraj, Muralidharan
AU  - Tatlisumak, Turgut
AU  - Amouyel, Philippe
AU  - Debette, Stéphanie
AU  - Rinkel, Gabriel J E
AU  - Worrall, Bradford B
AU  - Pera, Joanna
AU  - Slowik, Agnieszka
AU  - Gaál-Paavola, Emília I
AU  - Niemelä, Mika
AU  - Jääskeläinen, Juha E
AU  - von Und Zu Fraunberg, Mikael
AU  - Lindgren, Antti
AU  - Broderick, Joseph P
AU  - Werring, David J
AU  - Woo, Daniel
AU  - Redon, Richard
AU  - Bijlenga, Philippe
AU  - Kamatani, Yoichiro
AU  - Veldink, Jan H
AU  - Ruigrok, Ynte M
AU  - Bian, Zheng
AU  - Chen, Junshi
AU  - Chen, Yiping
AU  - Clarke, Robert
AU  - Collins, Rory
AU  - Guo, Yu
AU  - Han, Xiao
AU  - Hill, Michael
AU  - Liu, Depei
AU  - Lv, Jun
AU  - Millwood, Iona
AU  - Peto, Richard
AU  - Sansome, Sam
AU  - Walters, Robin
AU  - Yang, Xiaoming
AU  - Yu, Canqing
AU  - Bonner, Stephen
AU  - Walsh, Daniel
AU  - Bulters, Diederik
AU  - Kitchen, Neil
AU  - Brown, Martin
AU  - Grieve, Joan
AU  - Dichgans, Martin
TI  - Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
JO  - Nature genetics
VL  - 52
IS  - 12
SN  - 1546-1718
CY  - London
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2021-00136
SP  - 1303 - 1313
PY  - 2020
N1  - ISSN 1546-1718 not unique: **3 hits**.
AB  - 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.
KW  - Asian People: genetics
KW  - Asian Continental Ancestry Group: genetics
KW  - Blood Pressure: genetics
KW  - Case-Control Studies
KW  - Endothelial Cells: pathology
KW  - European Continental Ancestry Group: genetics
KW  - Genetic Predisposition to Disease: genetics
KW  - Genome-Wide Association Study
KW  - Humans
KW  - Hypertension: genetics
KW  - Hypertension: physiopathology
KW  - Intracranial Aneurysm: genetics
KW  - Intracranial Aneurysm: pathology
KW  - Polymorphism, Single Nucleotide: genetics
KW  - Risk Factors
KW  - Smoking: adverse effects
KW  - Smoking: genetics
KW  - Subarachnoid Hemorrhage: genetics
KW  - Subarachnoid Hemorrhage: pathology
KW  - White People: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:33199917
C2  - pmc:PMC7116530
DO  - DOI:10.1038/s41588-020-00725-7
UR  - https://pub.dzne.de/record/154282
ER  -