UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Bakker, MK; van der Spek, RAA; van Rheenen, W; Morel, S; Bourcier, R; Hostettler, IC; Alg, VS; ... Ruigrok, YM; + view all (2020) Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nature Genetics , 52 (12) pp. 1303-1313. 10.1038/s41588-020-00725-7. Green open access

[thumbnail of Werring_Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors_AAM.pdf]
Preview
Text
Werring_Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors_AAM.pdf - Accepted version

Download (407kB) | Preview

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.

Type: Article
Title: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-020-00725-7
Publisher version: https://doi.org/10.1038/s41588-020-00725-7
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Cerebrovascular disorders, Genome-wide association studies, Stroke
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10118562
Downloads since deposit
27Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item