Dataset Information

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

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.

SUBMITTER: Keene KL

PROVIDER: S-EPMC7387190 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Keene Keith L KL Hyacinth Hyacinth I HI Bis Joshua C JC Kittner Steven J SJ Mitchell Braxton D BD Cheng Yu-Ching YC Pare Guillaume G Chong Michael M O'Donnell Martin M Meschia James F JF Chen Wei-Min WM Sale Michèle M MM Rich Stephen S SS Nalls Mike A MA Zonderman Alan B AB Evans Michele K MK Wilson James G JG Correa Adolfo A Markus Hugh S HS Traylor Matthew M Lewis Cathryn M CM Carty Cara L CL Reiner Alexander A Haessler Jeff J Langefeld Carl D CD Gottesman Rebecca R Mosley Thomas H TH Woo Daniel D Yaffe Kristine K Liu YongMei Y Longstreth William T WT Psaty Bruce M BM Kooperberg Charles C Lange Leslie A LA Sacco Ralph R Rundek Tatjana T Lee Jin-Moo JM Cruchaga Carlos C Furie Karen L KL Arnett Donna K DK Benavente Oscar R OR Grewal Raji P RP Peddareddygari Leema Reddy LR Dichgans Martin M Malik Rainer R Worrall Bradford B BB Fornage Myriam M

Stroke 20200722 8

<h4>Background and purpose</h4>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.<h4>Methods</h4>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.<h4 ...[more]

PMID: 32693751

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Dataset Information

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

Background and purpose

Methods

Results

Conclusions

Publications

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

Similar Datasets

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