Citations 1
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. , Cheng, Yu-Ching , O’Donnell, Martin , Chen, Wei‐Min , Sale, Michèle M. , Rich, Stephen S. , Nalls, Mike A., Wilson, James G. , Markus, Hugh S. , Lewis, Cathryn M. , Carty, Cara L. , Reiner, Alex P. , Haessler, Jeff, Langefeld, Carl D. , Gottesman, Rebecca F., Woo, Daniel , Yaffe, Kristine , Liu, YongMei, Longstreth, W.T. , Kooperberg, Charles, Lange, Leslie A., Sacco, Ralph L., Cruchaga, Carlos , Furie, Karen L., Arnett, Donna K. , Benavente, Oscar, Grewal, Raji P., Peddareddygari, Leema Reddy , Dichgans, Martin , Worrall, Bradford B. , Fornage, Myriam , Consortia, on behalf of the COMPASS, SiGN, and METASTROKE, Dichgans, Martin , Cruchaga, Carlos , Rich, Stephen S , Arnett, Donna K , Lewis, Cathryn M , Mitchell, Braxton D. , Paré, Guillaume , Chong, Michael , Meschia, James F. , Zonderman, Alan B. , Evans, Michele K. , Correa, Adolfo , Traylor, Matthew , Mosley, Thomas H. , Psaty, Bruce M. , Rundek, Tatjana , Lee, Jin‐Moo , Malik, Rainer , Consortia, on behalf of the COMPASS, SiGN, and METASTROKE
Stroke | July 22, 2020 | Volume: 51 | Issue: 8 | Pages: 2454-2463
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.