Publikation

Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.

Wissenschaftlicher Artikel/Review - 16.11.2020

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PubMed
DOI
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Zitation
Ruigrok Y, Sargurupremraj M, Dichgans M, Malik R, Klijn C, Zaroff J, Breen G, Coleman J, Kim H, Ko N, Bown M, Jones G, ĀăąĆĉČĎ Ā, Martin O, Dauvillier J, Schilling S, Hirsch S, Tatlisumak T, Amouyel P, Debette S, Veldink J, Kamatani Y, Bijlenga P, Redon R, Woo D, Werring D, Broderick J, Lindgren A, von Und Zu Fraunberg M, Jaaskelainen J, Niemelä M, Gaal-Paavola E, Slowik A, Pera J, Worrall B, Rinkel G, Friedrich C, Verschuren W, Zwart J, Chen Z, Millwood I, Liang L, Lin K, Walters R, Matsuda K, Terao C, Akiyama M, Koido M, van Eijk K, Alg V, Hostettler I, Bourcier R, Morel S, van Rheenen W, van der Spek R, Rouleau G, Zhou S, Rannikmäe K, Hveem K, Willer C, Sandvei M, Brumpton B, Johnsen M, Børte S, Winsvold B, Desal H, Eugène F, Shotar E, Gentric J, Naggara O, Dina C, van den Berg L, Houlden H, Sudlow C, Bakker M. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nat Genet 2020; 52:1303-1313.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Nat Genet 2020; 52
Veröffentlichungsdatum
16.11.2020
eISSN (Online)
1546-1718
Seiten
1303-1313
Kurzbeschreibung/Zielsetzung

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.