Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke
Open Access
- 1 August 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 51 (8), 2454-2463
- https://doi.org/10.1161/strokeaha.120.029123
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−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.Keywords
This publication has 48 references indexed in Scilit:
- Genetic Heritability of Ischemic Stroke and the Contribution of Previously Reported Candidate Gene and Genomewide AssociationsStroke, 2012
- Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studiesThe Lancet Neurology, 2012
- Common variants at 6p21.1 are associated with large artery atherosclerotic strokeNature Genetics, 2012
- Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic strokeNature Genetics, 2012
- Genome-Wide Association Analysis of Ischemic Stroke in Young AdultsG3 Genes|Genomes|Genetics, 2011
- Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney diseaseKidney International, 2011
- METAL: fast and efficient meta-analysis of genomewide association scansBioinformatics, 2010
- Validation Study of Genetic Associations with Coronary Artery Disease on Chromosome 3q13‐21 and Potential Effect Modification by SmokingAnnals of Human Genetics, 2009
- Genomewide Association Studies of StrokeThe New England Journal of Medicine, 2009
- Peakwide Mapping on Chromosome 3q13 Identifies the Kalirin Gene as a Novel Candidate Gene for Coronary Artery DiseaseAmerican Journal of Human Genetics, 2007