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

for the MEGASTROKE consortium and the International Stroke Genetics Consortium

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)934-939
Number of pages6
JournalAnnals of neurology
Volume84
Issue number6
DOIs
StatePublished - Dec 2018

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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