Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke. Issue 8 (August 2020)

• Record Type: Journal Article
• Authors: 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;
• Is Part Of: Stroke. Volume 51:Issue 8(2020)
• Publication Date: 2020-08
• Subjects: brain ischemia -- coronary artery disease -- genome-wide association study -- meta-analysis -- phenotype -- risk factors; Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.120.029123
• Languages: English
• ISSNs: 0039-2499

Abstract

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. Abstract : Supplemental Digital Content is available in the text.