Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci.

ABSTRACT: Ischaemic stroke is a common complication of sickle cell disease (SCD) and without intervention can affect 11% of children with SCD before the age of 20. Within the Trans-Omics for Precision Medicine (TOPMed), a genome-wide association study (GWAS) of ischaemic stroke was performed on 1333 individuals with SCD from Brazil (178 cases, 1155 controls). Via a novel Cox proportional-hazards analysis, we searched for variants associated with ischaemic stroke occurring at younger ages. Variants at genome-wide significance (p < 5 × 10^-8 ) include two near genes previously linked to non-SCD early-onset stroke (<65 years): ADAMTS2 (rs147625068, p = 3.70 × 10^-9 ) and CDK18 (rs12144136, p = 2.38 × 10^-9 ). Meta-analysis, which included the independent SCD cohorts Walk-P

SUBMITTER: Earley EJ 

PROVIDER: S-EPMC10155195 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature