Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke

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] = 1.0...

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Main Authors: Malik, R, Rannikmäe, K, Traylor, M, Georgakis, M, Sargurupremraj, M, Markus, H, Hopewell, J, Debette, S, Sudlow, C, Dichgans, M
Format: Journal article
Language:English
Published: Wiley 2018
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author Malik, R
Rannikmäe, K
Traylor, M
Georgakis, M
Sargurupremraj, M
Markus, H
Hopewell, J
Debette, S
Sudlow, C
Dichgans, M
author_facet Malik, R
Rannikmäe, K
Traylor, M
Georgakis, M
Sargurupremraj, M
Markus, H
Hopewell, J
Debette, S
Sudlow, C
Dichgans, M
author_sort Malik, R
collection OXFORD
description 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.
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spelling oxford-uuid:2ab274c9-256b-43e0-9155-44973ca66c372022-03-26T12:26:39ZGenome‐wide meta‐analysis identifies 3 novel loci associated with strokeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2ab274c9-256b-43e0-9155-44973ca66c37EnglishSymplectic Elements at OxfordWiley2018Malik, RRannikmäe, KTraylor, MGeorgakis, MSargurupremraj, MMarkus, HHopewell, JDebette, SSudlow, CDichgans, MWe 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.
spellingShingle Malik, R
Rannikmäe, K
Traylor, M
Georgakis, M
Sargurupremraj, M
Markus, H
Hopewell, J
Debette, S
Sudlow, C
Dichgans, M
Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke
title Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke
title_full Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke
title_fullStr Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke
title_full_unstemmed Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke
title_short Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke
title_sort genome wide meta analysis identifies 3 novel loci associated with stroke
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