Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.
Asian People
/ genetics
Blood Pressure
/ genetics
Case-Control Studies
Endothelial Cells
/ pathology
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
Humans
Hypertension
/ genetics
Intracranial Aneurysm
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Risk Factors
Smoking
/ adverse effects
Subarachnoid Hemorrhage
/ genetics
White People
/ genetics
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
24
02
2020
accepted:
24
09
2020
pubmed:
18
11
2020
medline:
26
1
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33199917
doi: 10.1038/s41588-020-00725-7
pii: 10.1038/s41588-020-00725-7
pmc: PMC7116530
mid: EMS108003
doi:
Banques de données
figshare
['10.6084/m9.figshare.11303372']
ClinicalTrials.gov
['NCT02848495']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1303-1313Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212946/Z/18/Z
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12026/2
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202922
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Organisme : Medical Research Council
ID : MC_UU_00017/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137686851
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14135
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202922/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-PC-14135
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13049
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 088158/Z/09/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R01 NS034949
Pays : United States
Organisme : Wellcome Trust
ID : 104085/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S004130/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 088158
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104085
Pays : United Kingdom
Investigateurs
Zheng Bian
(Z)
Junshi Chen
(J)
Yiping Chen
(Y)
Robert Clarke
(R)
Rory Collins
(R)
Yu Guo
(Y)
Xiao Han
(X)
Michael Hill
(M)
Depei Liu
(D)
Jun Lv
(J)
Iona Millwood
(I)
Richard Peto
(R)
Sam Sansome
(S)
Robin Walters
(R)
Xiaoming Yang
(X)
Canqing Yu
(C)
Stephen Bonner
(S)
Daniel Walsh
(D)
Diederik Bulters
(D)
Neil Kitchen
(N)
Martin Brown
(M)
Joan Grieve
(J)
Martin Dichgans
(M)
Commentaires et corrections
Type : ErratumIn
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