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

Publication ,  Journal Article
Keene, KL; Hyacinth, HI; Bis, JC; Kittner, SJ; Mitchell, BD; Cheng, Y-C; Pare, G; Chong, M; O'Donnell, M; Meschia, JF; Chen, W-M; Sale, MM ...
Published in: Stroke
August 2020

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.

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Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

August 2020

Volume

51

Issue

8

Start / End Page

2454 / 2463

Location

United States

Related Subject Headings

  • Stroke
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Cohort Studies
  • Black or African American
  • 4201 Allied health and rehabilitation science
  • 3209 Neurosciences
 

Citation

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Keene, K. L., Hyacinth, H. I., Bis, J. C., Kittner, S. J., Mitchell, B. D., Cheng, Y.-C., … COMPASS, SiGN, and METASTROKE Consortia, . (2020). Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke. Stroke, 51(8), 2454–2463. https://doi.org/10.1161/STROKEAHA.120.029123
Keene, Keith L., Hyacinth I. Hyacinth, Joshua C. Bis, Steven J. Kittner, Braxton D. Mitchell, Yu-Ching Cheng, Guillaume Pare, et al. “Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke.Stroke 51, no. 8 (August 2020): 2454–63. https://doi.org/10.1161/STROKEAHA.120.029123.
Keene KL, Hyacinth HI, Bis JC, Kittner SJ, Mitchell BD, Cheng Y-C, et al. Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke. Stroke. 2020 Aug;51(8):2454–63.
Keene, Keith L., et al. “Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke.Stroke, vol. 51, no. 8, Aug. 2020, pp. 2454–63. Pubmed, doi:10.1161/STROKEAHA.120.029123.
Keene KL, Hyacinth HI, Bis JC, Kittner SJ, Mitchell BD, Cheng Y-C, Pare G, Chong M, O’Donnell M, Meschia JF, Chen W-M, Sale MM, Rich SS, Nalls MA, Zonderman AB, Evans MK, Wilson JG, Correa A, Markus HS, Traylor M, Lewis CM, Carty CL, Reiner A, Haessler J, Langefeld CD, Gottesman R, Mosley TH, Woo D, Yaffe K, Liu Y, Longstreth WT, Psaty BM, Kooperberg C, Lange LA, Sacco R, Rundek T, Lee J-M, Cruchaga C, Furie KL, Arnett DK, Benavente OR, Grewal RP, Peddareddygari LR, Dichgans M, Malik R, Worrall BB, Fornage M, COMPASS, SiGN, and METASTROKE Consortia. Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke. Stroke. 2020 Aug;51(8):2454–2463.

Published In

Stroke

DOI

EISSN

1524-4628

Publication Date

August 2020

Volume

51

Issue

8

Start / End Page

2454 / 2463

Location

United States

Related Subject Headings

  • Stroke
  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Cohort Studies
  • Black or African American
  • 4201 Allied health and rehabilitation science
  • 3209 Neurosciences