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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Malik, Rainer 
Rannikmäe, Kristiina 
Georgakis, Marios K 
Sargurupremraj, Muralidharan 

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.

Description

Keywords

Collagen Type IV, Databases, Factual, Europe, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Nitric Oxide Synthase Type III, Protein Serine-Threonine Kinases, Protein-Tyrosine Kinases, Risk Factors, Stroke, Dyrk Kinases

Journal Title

Ann Neurol

Conference Name

Journal ISSN

0364-5134
1531-8249

Volume Title

84

Publisher

Wiley