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

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, Michele 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. und Fornage, Myriam (2020): Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke. In: Stroke, Vol. 51, No. 8: pp. 2454-2463

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 2x to 3x 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 theHNF1Agene that reached genome-wide significance (P=4.62x10(-8)) and an additional 29 variants with suggestive evidence of association (P<1x10(-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 correctionPvalue of 2.08x10(-3)(0.05/24 unique loci), we were able to validate associations at theHNF1Alocus in both SiGN (P=8.18x10(-4)) and METASTROKE (P=1.72x10(-3)) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in theHNF1Agene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in theSFXN4andTMEM108genes 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.

• Item Type: Journal article
• Faculties: Medicine; Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Institute for Stroke and Dementia Research (ISD)
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0039-2499
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198