Format

Send to

Choose Destination
Ann Neurol. 2018 Dec;84(6):934-939. doi: 10.1002/ana.25369. Epub 2018 Nov 30.

Genome-wide meta-analysis identifies 3 novel loci associated with stroke.

Author information

1
Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
2
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
3
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
4
Stroke Research Group, Division of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
5
INSERM U1219, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.
6
Department of Neurology, Institute for Neurodegenerative Disease, Bordeaux University Hospital, Bordeaux, France.
7
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
8
Munich Cluster for Systems Neurology, Munich, Germany.
9
German Center for Neurodegenerative Diseases, Munich, Germany.

Abstract

We conducted a European-only and transancestral genome-wide association meta-analysis in 72,147 stroke patients and 823,869 controls using data from UK Biobank (UKB) and the MEGASTROKE consortium. We identified an exonic polymorphism in NOS3 (rs1799983, p.Glu298Asp; p = 2.2E-8, odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.04-1.07) and variants in an intron of COL4A1 (rs9521634; p = 3.8E-8, OR = 1.04, 95% CI = 1.03-1.06) and near DYRK1A (rs720470; p = 6.1E-9, OR = 1.05, 95% CI = 1.03-1.07) at genome-wide significance for stroke. Effect sizes of known stroke loci were highly correlated between UKB and MEGASTROKE. Using Mendelian randomization, we further show that genetic variation in the nitric oxide synthase-nitric oxide pathway in part affects stroke risk via variation in blood pressure. Ann Neurol 2018;84:934-939.

PMID:
30383316
PMCID:
PMC6644297
DOI:
10.1002/ana.25369
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center