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

Ann Neurol. 2018 Dec;84(6):934-939. doi: 10.1002/ana.25369. Epub 2018 Nov 30.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Collagen Type IV / genetics*
  • Databases, Factual / statistics & numerical data
  • Europe
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Nitric Oxide Synthase Type III / genetics*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Risk Factors
  • Stroke / genetics*

Substances

  • COL4A1 protein, human
  • Collagen Type IV
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases