| Literature DB >> 33199917 |
Mark K Bakker1, Rick A A van der Spek2, Wouter van Rheenen2, Sandrine Morel3,4, Romain Bourcier5,6, Isabel C Hostettler7,8, Varinder S Alg7, Kristel R van Eijk2, Masaru Koido9,10, Masato Akiyama9,11,12, Chikashi Terao9, Koichi Matsuda13,14, Robin G Walters15,16, Kuang Lin15, Liming Li17, Iona Y Millwood15,16, Zhengming Chen15,16, Guy A Rouleau18, Sirui Zhou19, Kristiina Rannikmäe20, Cathie L M Sudlow20,21, Henry Houlden22, Leonard H van den Berg2, Christian Dina5, Olivier Naggara23,24, Jean-Christophe Gentric25, Eimad Shotar26, François Eugène27, Hubert Desal5,6, Bendik S Winsvold28,29, Sigrid Børte29,30,31, Marianne Bakke Johnsen29,30,31, Ben M Brumpton29, Marie Søfteland Sandvei32,33, Cristen J Willer34, Kristian Hveem29,35, John-Anker Zwart28,29,31, W M Monique Verschuren36,37, Christoph M Friedrich38,39, Sven Hirsch40, Sabine Schilling40, Jérôme Dauvillier41, Olivier Martin41, Gregory T Jones42, Matthew J Bown43,44, Nerissa U Ko45, Helen Kim46,47,48, Jonathan R I Coleman49,50, Gerome Breen49,50, Jonathan G Zaroff51, Catharina J M Klijn52, Rainer Malik53, Martin Dichgans54,55, Muralidharan Sargurupremraj56,57, Turgut Tatlisumak58, Philippe Amouyel59, Stéphanie Debette56,57, Gabriel J E Rinkel2, Bradford B Worrall60, Joanna Pera61, Agnieszka Slowik61, Emília I Gaál-Paavola62,63, Mika Niemelä62, Juha E Jääskeläinen64,65, Mikael von Und Zu Fraunberg64,65, Antti Lindgren64,65, Joseph P Broderick66, David J Werring7, Daniel Woo66, Richard Redon5, Philippe Bijlenga4, Yoichiro Kamatani9,13, Jan H Veldink2, Ynte M Ruigrok67.
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.Entities:
Mesh：
Year: 2020 PMID： 33199917 PMCID： PMC7116530 DOI： 10.1038/s41588-020-00725-7
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307