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

Details

Serval ID
serval:BIB_9D97AC434D8D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
Journal
Nature genetics
Author(s)
Bakker M.K., van der Spek RAA, van Rheenen W., Morel S., Bourcier R., Hostettler I.C., Alg V.S., van Eijk K.R., Koido M., Akiyama M., Terao C., Matsuda K., Walters R.G., Lin K., Li L., Millwood I.Y., Chen Z., Rouleau G.A., Zhou S., Rannikmäe K., Sudlow CLM, Houlden H., van den Berg L.H., Dina C., Naggara O., Gentric J.C., Shotar E., Eugène F., Desal H., Winsvold B.S., Børte S., Johnsen M.B., Brumpton B.M., Sandvei M.S., Willer C.J., Hveem K., Zwart J.A., Verschuren WMM, Friedrich C.M., Hirsch S., Schilling S., Dauvillier J., Martin O., Jones G.T., Bown M.J., Ko N.U., Kim H., Coleman JRI, Breen G., Zaroff J.G., Klijn CJM, Malik R., Dichgans M., Sargurupremraj M., Tatlisumak T., Amouyel P., Debette S., Rinkel GJE, Worrall B.B., Pera J., Slowik A., Gaál-Paavola E.I., Niemelä M., Jääskeläinen J.E., von Und Zu Fraunberg M., Lindgren A., Broderick J.P., Werring D.J., Woo D., Redon R., Bijlenga P., Kamatani Y., Veldink J.H., Ruigrok Y.M.
Working group(s)
HUNT All-In Stroke, China Kadoorie Biobank Collaborative Group, BioBank Japan Project Consortium, ICAN Study Group, CADISP Group, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators, International Stroke Genetics Consortium (ISGC)
Contributor(s)
Bian Z., Chen J., Chen Y., Clarke R., Collins R., Guo Y., Han X., Hill M., Liu D., Lv J., Millwood I., Peto R., Sansome S., Walters R., Yang X., Yu C., Bonner S., Walsh D., Bulters D., Kitchen N., Brown M., Grieve J., Dichgans M.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
12/2020
Peer-reviewed
Oui
Volume
52
Number
12
Pages
1303-1313
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Asian People/genetics, Blood Pressure/genetics, Case-Control Studies, Endothelial Cells/pathology, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Humans, Hypertension/genetics, Hypertension/physiopathology, Intracranial Aneurysm/genetics, Intracranial Aneurysm/pathology, Polymorphism, Single Nucleotide/genetics, Risk Factors, Smoking/adverse effects, Smoking/genetics, Subarachnoid Hemorrhage/genetics, Subarachnoid Hemorrhage/pathology, White People/genetics
Pubmed
Web of science
Create date
23/11/2020 14:44
Last modification date
16/04/2024 7:11
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