{"doi":"10.1111/bjh.18637","title":"Genome‐wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates <i>ADAMTS2</i> and <i>CDK18</i> and uncovers novel loci","abstract":"Summary 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 &lt; 5 × 10 −8 ) include two near genes previously linked to non‐SCD early‐onset stroke (&lt;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‐PHaSST and PUSH, exhibited consistent association for variants rs1209987 near gene TBC1D32 ( p = 3.36 × 10 −10 ), rs188599171 near CUX1 ( p = 5.89 × 10 −11 ), rs77900855 near BTG1 ( p = 4.66 × 10 −8 ), and rs141674494 near VPS13C (1.68 × 10 −9 ). Findings from this study support a multivariant model of early ischaemic stroke risk and possibly a shared genetic architecture between SCD individuals and non‐SCD individuals younger than 65 years.","journal":"British Journal of Haematology","year":2023,"id":363361,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9165,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":387946,"name":"Shannon Kelly","orcid":"0000-0003-2049-3992","position":1,"is_corresponding":false},{"id":321167,"name":"Fang Fang","orcid":"0000-0001-9829-2934","position":2,"is_corresponding":false},{"id":387947,"name":"Cecília Salete Alencar","orcid":"0000-0002-3583-2275","position":3,"is_corresponding":false},{"id":387943,"name":"Daniela de Oliveira Werneck Rodrigues","orcid":"0000-0003-3062-2954","position":4,"is_corresponding":false},{"id":1117390,"name":"Dahra Teles Soares Cruz","orcid":"0000-0001-8047-6583","position":5,"is_corresponding":false},{"id":573776,"name":"Jonathan M. Flanagan","orcid":"0000-0003-1330-6618","position":6,"is_corresponding":false},{"id":310457,"name":"Russell E. Ware","orcid":"0000-0001-9582-0594","position":7,"is_corresponding":false},{"id":351694,"name":"Xu Zhang","orcid":"0000-0002-7732-1385","position":8,"is_corresponding":false},{"id":269831,"name":"Victor R. Gordeuk","orcid":"0000-0003-4725-7295","position":9,"is_corresponding":false},{"id":24963,"name":"Mark T. Gladwin","orcid":"0000-0001-7267-9006","position":10,"is_corresponding":false},{"id":288811,"name":"Yingze Zhang","orcid":"0000-0001-6947-2901","position":11,"is_corresponding":false},{"id":270743,"name":"Mehdi Nouraie","orcid":"0000-0001-7465-0581","position":12,"is_corresponding":false},{"id":24998,"name":"Sergeï Nekhai","orcid":"0000-0003-0744-7887","position":13,"is_corresponding":false},{"id":149534,"name":"Ester Sabino","orcid":"0000-0003-2623-5126","position":14,"is_corresponding":false},{"id":24721,"name":"Brian Custer","orcid":"0000-0001-6251-366X","position":15,"is_corresponding":false},{"id":484627,"name":"Carla Luana Dinardo","orcid":"0000-0002-0453-7863","position":16,"is_corresponding":false},{"id":73865,"name":"Grier P. Page","orcid":"0000-0003-2582-3786","position":17,"is_corresponding":false},{"id":409112,"name":"Eric J. Earley","orcid":"0000-0001-6576-1319","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:14:28.054440Z","pmid":"36602125","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}