Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.
Malik R, Chauhan G, Traylor M et al.
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Abstract
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Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
40,585 European ancestry cases, 406,111 European ancestry controls, 17,369 East Asian ancestry cases, 28,195 East Asian ancestry controls, 2,437 South Asian ancestry cases, 6,707 South Asian ancestry controls, 5,541 African American cases, 15,154 African American controls, 365 Asian ancestry cases, 333 Asian ancestry controls, 865 Latin American cases, 692 Latin American controls
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