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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Autores principales: Malik, Rainer, Rannikmäe, Kristiina, Traylor, Matthew, Georgakis, Marios K., Sargurupremraj, Muralidharan, Markus, Hugh S., Hopewell, Jemma C., Debette, Stephanie, Sudlow, Cathie L. M., Dichgans, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2018
Materias:
Brief Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644297/
https://www.ncbi.nlm.nih.gov/pubmed/30383316
http://dx.doi.org/10.1002/ana.25369
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author Malik, Rainer
Rannikmäe, Kristiina
Traylor, Matthew
Georgakis, Marios K.
Sargurupremraj, Muralidharan
Markus, Hugh S.
Hopewell, Jemma C.
Debette, Stephanie
Sudlow, Cathie L. M.
Dichgans, Martin
author_facet Malik, Rainer
Rannikmäe, Kristiina
Traylor, Matthew
Georgakis, Marios K.
Sargurupremraj, Muralidharan
Markus, Hugh S.
Hopewell, Jemma C.
Debette, Stephanie
Sudlow, Cathie L. M.
Dichgans, Martin
author_sort Malik, Rainer
collection PubMed
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. Ann Neurol 2018;84:934–939
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spelling pubmed-66442972019-07-31 Genome‐wide meta‐analysis identifies 3 novel loci associated with stroke Malik, Rainer Rannikmäe, Kristiina Traylor, Matthew Georgakis, Marios K. Sargurupremraj, Muralidharan Markus, Hugh S. Hopewell, Jemma C. Debette, Stephanie Sudlow, Cathie L. M. Dichgans, Martin Ann Neurol Brief Communications 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 John Wiley & Sons, Inc. 2018-11-30 2018-12 /pmc/articles/PMC6644297/ /pubmed/30383316 http://dx.doi.org/10.1002/ana.25369 Text en © 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Brief Communications
Malik, Rainer
Rannikmäe, Kristiina
Traylor, Matthew
Georgakis, Marios K.
Sargurupremraj, Muralidharan
Markus, Hugh S.
Hopewell, Jemma C.
Debette, Stephanie
Sudlow, Cathie L. M.
Dichgans, Martin
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
topic Brief Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644297/
https://www.ncbi.nlm.nih.gov/pubmed/30383316
http://dx.doi.org/10.1002/ana.25369
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