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.
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.
In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the
HNF1Agene 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 Pvalue of 2.08×10 −3 (0.05/24 unique loci), we were able to validate associations at the HNF1Alocus 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 HNF1Agene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4and TMEM108genes 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.