Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke-Reference-Cited by-同舟云学术

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

Published:2020-08 Issue:8 Volume:51 Page:2454-2463
ISSN:0039-2499
Container-title:Stroke
language:en
Short-container-title:Stroke

Author:

Keene Keith L.¹^ORCID,Hyacinth Hyacinth I.²,Bis Joshua C.³,Kittner Steven J.⁴,Mitchell Braxton D.⁴,Cheng Yu-Ching⁴,Pare Guillaume⁵,Chong Michael⁵,O’Donnell Martin⁶,Meschia James F.⁷,Chen Wei-Min⁸,Sale Michèle M.⁸,Rich Stephen S.⁸,Nalls Mike A.⁹¹⁰,Zonderman Alan B.¹¹,Evans Michele K.¹¹,Wilson James G.¹²,Correa Adolfo¹²,Markus Hugh S.¹³,Traylor Matthew¹⁴,Lewis Cathryn M.¹⁵,Carty Cara L.¹⁶,Reiner Alexander¹⁷,Haessler Jeff¹⁷,Langefeld Carl D.¹⁸,Gottesman Rebecca¹⁹,Mosley Thomas H.¹²,Woo Daniel²⁰,Yaffe Kristine²¹,Liu YongMei¹⁸,Longstreth William T.³,Psaty Bruce M.²²²³,Kooperberg Charles¹⁷,Lange Leslie A.²⁴,Sacco Ralph²⁵,Rundek Tatjana²⁵,Lee Jin-Moo²⁶,Cruchaga Carlos²⁶,Furie Karen L.²⁷,Arnett Donna K.²⁸,Benavente Oscar R.²⁹,Grewal Raji P.³⁰,Peddareddygari Leema Reddy³⁰,Dichgans Martin³¹³²,Malik Rainer³¹,Worrall Bradford B.³³,Fornage Myriam³⁴,

Affiliation:

1. Department of Biology; Brody School of Medicine Center for Health Disparities, East Carolina University, Greenville, NC (K.L.K.).

2. Aflac Cancer and Blood Disorder Center of Emory University and Children’s Healthcare of Atlanta University, GA (H.I.H.).

3. University of Washington, Seattle, WA (J.C.B., W.T.L.).

4. Baltimore Veterans Administration Medical Center and University of Maryland School of Medicine, Baltimore, MD (S.J.K., B.D.M., Y.-C.C.).

5. McMaster University and Population Health Research Institute, Hamilton Ontario (G.P., M.C.).

6. National University of Ireland Galway, Ireland (M.O.).

7. Mayo Clinic Florida, Jacksonville (J.F.M.).

8. Center for Public Health Genomics, University of Virginia, Charlottesville (W.-M.C., M.M.S., S.S.R.).

9. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD (M.A.N.).

10. Data Tecnica International, Glen Echo, MD (M.A.N.).

11. Laboratory of Epidemiology and Population Science, National Institute on Aging, Baltimore, MD (A.B.Z., M.K.E.).

12. University of Mississippi Medical Center, Jackson (J.G.W., A.C., T.H.M.).

13. University of Cambridge, England, United Kingdom (H.S.M.).

14. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (M.T.).

15. Social, Genetic and Developmental Psychiatry Centre, King’s College London, United Kingdom (C.M.L.).

16. Initiative for Research and Education to Advance Community Health, Washington State University, Seattle (C.L.C.).

17. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (A.R., J.H., C.K.).

18. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC (C.D.L., C.L.).

19. Johns Hopkins University School of Medicine, Baltimore, MD (R.G.).

20. Department of Neurology, University of Cincinnati, OH (D.W.).

21. University of California, San Francisco (K.Y.).

22. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle (B.M.P.).

23. Kaiser Permanente Washington Health Research Institute, Seattle, WA (B.M.P.).

24. University of Colorado Anschutz Medical Campus, Denver (L.A.L.).

25. University of Miami, Miller School of Medicine, FL (R.S., T.R.).

26. Washington University School of Medicine, St. Louis, MO (J.-M.L., C.C.).

27. Brown University Warren Alpert Medical School, Providence, RI (K.L.F.).

28. University of Kentucky, College of Public Health, Lexington (D.K.A.).

29. University of British Columbia, Vancouver, (O.R.B.).

30. Neuroscience Institute, Saint Francis Medical Center, Trenton, NJ (R.P.G., L.R.P.).

31. Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Germany (M.D., R.M.).

32. Munich Cluster for Systems Neurology (SyNergy), Germany (M.D.).

33. Department of Neurology, University of Virginia, Charlottesville (B.B.W.).

34. Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston (M.F.).

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialised Nursing,Cardiology and Cardiovascular Medicine,Clinical Neurology

Reference47 articles.

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