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

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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.

authors

  • O'Donnell, Martin
  • Keene, Keith L
  • Hyacinth, Hyacinth I
  • Bis, Joshua C
  • Kittner, Steven J
  • Mitchell, Braxton D
  • Cheng, Yu-Ching
  • Pare, Guillaume
  • Chong, Michael
  • O’Donnell, Martin
  • Meschia, James F
  • Chen, Wei-Min
  • Sale, Michèle M
  • Rich, Stephen S
  • Nalls, Mike A
  • Zonderman, Alan B
  • Evans, Michele K
  • Wilson, James G
  • Correa, Adolfo
  • Markus, Hugh S
  • Traylor, Matthew
  • Lewis, Cathryn M
  • Carty, Cara L
  • Reiner, Alexander
  • Haessler, Jeff
  • Langefeld, Carl D
  • Gottesman, Rebecca
  • Mosley, Thomas H
  • Woo, Daniel
  • Yaffe, Kristine
  • Liu, YongMei
  • Longstreth, William T
  • Psaty, Bruce M
  • Kooperberg, Charles
  • Lange, Leslie A
  • Sacco, Ralph
  • Rundek, Tatjana
  • Lee, Jin-Moo
  • Cruchaga, Carlos
  • Furie, Karen L
  • Arnett, Donna K
  • Benavente, Oscar R
  • Grewal, Raji P
  • Peddareddygari, Leema Reddy
  • Dichgans, Martin
  • Malik, Rainer
  • Worrall, Bradford B
  • Fornage, Myriam

publication date

  • August 2020

published in