TY - JOUR
T1 - Genome-wide meta-analysis identifies 3 novel loci associated with stroke
AU - for the MEGASTROKE consortium and the International Stroke Genetics Consortium
AU - Malik, Rainer
AU - Rannikmäe, Kristiina
AU - Traylor, Matthew
AU - Georgakis, Marios K.
AU - Sargurupremraj, Muralidharan
AU - Markus, Hugh S.
AU - Hopewell, Jemma C.
AU - Debette, Stephanie
AU - Sudlow, Cathie L.M.
AU - Dichgans, Martin
N1 - Publisher Copyright:
© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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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U2 - 10.1002/ana.25369
DO - 10.1002/ana.25369
M3 - Article
C2 - 30383316
AN - SCOPUS:85057859433
SN - 0364-5134
VL - 84
SP - 934
EP - 939
JO - Annals of neurology
JF - Annals of neurology
IS - 6
ER -