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

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 gene that reached genome-wide significance (=4.62×10) and an additional 29 variants with suggestive evidence of association (<1×10), 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 value of 2.08×10 (0.05/24 unique loci), we were able to validate associations at the locus in both SiGN (=8.18×10) and METASTROKE (=1.72×10) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the and 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.