Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke

COMPASS, SiGN, and METASTROKE Consortia

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26 Citations (Scopus)

Abstract

Background and Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans. Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts. Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the HNF1A gene that reached genome-wide significance (P=4.62×10 -8) and an additional 29 variants with suggestive evidence of association (P<1×10 -6), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction P value of 2.08×10 -3(0.05/24 unique loci), we were able to validate associations at the HNF1A locus in both SiGN (P=8.18×10 -4) and METASTROKE (P=1.72×10 -3) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the HNF1A gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4 and TMEM108 genes represent potential novel ischemic stroke loci. Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.

Original languageEnglish
Pages (from-to)2454-2463
Number of pages10
JournalStroke
Volume51
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

Keywords

  • brain ischemia
  • coronary artery disease
  • genome-wide association study
  • meta-analysis
  • phenotype
  • risk factors

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