Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans.

Autor: Akinyemi RO; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.; Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Tiwari HK; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Srinivasasainagendra V; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Akpa O; Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Sarfo FS; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Akpalu A; Department of Medicine, University of Ghana Medical School, Accra, Ghana., Wahab K; Department of Medicine, University of Ilorin Teaching Hospital, Ilorin, Nigeria., Obiako R; Department of Medicine, Ahmadu Bello University, Zaria, Nigeria., Komolafe M; Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria., Owolabi L; Department of Medicine, Aminu Kano Teaching Hospital, Kano, Nigeria., Osaigbovo GO; Jos University Teaching Hospital, Jos, Nigeria., Mamaeva OA; Department of Epidemiology, School of Public Health University of Alabama at Birmingham, Birmingham, USA., Halloran BA; Department of Pediatrics, Volker Hall University of Alabama at Birmingham, Birmingham, USA., Akinyemi J; Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Ibadan, Nigeria., Lackland D; Medical University of South Carolina, Charleston, SC, USA., Obiabo OY; Delta State University/Delta State University Teaching Hospital, Oghara, Nigeria., Sunmonu T; Department of Medicine, Federal Medical Centre, Ondo State, Owo, Nigeria., Chukwuonye II; Department of Medicine, Federal Medical Centre Umuahia, Abia State, Umuahia, Nigeria., Arulogun O; Department of Health Education, Faculty of Public Health, University of Ibadan, Ibadan, Nigeria., Jenkins C; Medical University of South Carolina, Charleston, SC, USA., Adeoye A; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Agunloye A; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Ogah OS; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Ogbole G; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Fakunle A; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.; Department of Public Health, College of Health Sciences, Osun State University, Osogbo, Nigeria., Uvere E; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Coker MM; Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria.; Genetics and Cell Biology Unit, Department of Zoology, Faculty of Science, University of Ibadan, Ibadan, Nigeria., Okekunle A; Department of Food and Nutrition, Seoul National University, Seoul, South Korea., Asowata O; Department of Epidemiology and Medical Statistics, College of Medicine, University of Ibadan, Ibadan, Nigeria., Diala S; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Ogunronbi M; Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria., Adeleye O; Department of Medicine, Federal Medical Centre, Abeokuta, Nigeria., Laryea R; Department of Medicine, University of Ghana Medical School, Accra, Ghana., Tagge R; Weill Institute for Neurosciences, School of Medicine, University of California San-Francisco, San Francisco, USA., Adeniyi S; Department of Medicine, University of Ilorin Teaching Hospital, Ilorin, Nigeria., Adusei N; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Oguike W; Department of Medicine, Ahmadu Bello University, Zaria, Nigeria., Olowoyo P; Federal Teaching Hospital, Ido-Ekiti, Ekiti State, Nigeria., Adebajo O; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Olalere A; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Oladele O; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Yaria J; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Fawale B; Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria., Ibinaye P; Department of Medicine, Ahmadu Bello University, Zaria, Nigeria., Oyinloye O; Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria., Mensah Y; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Oladimeji O; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Akpalu J; Department of Medicine, University of Ghana Medical School, Accra, Ghana., Calys-Tagoe B; Department of Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Dambatta HA; Department of Medicine, Aminu Kano Teaching Hospital, Kano, Nigeria., Ogunniyi A; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria., Kalaria R; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Arnett D; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, USA., Rotimi C; Center for Genomics and Global Health, National Human Genome Research Institute, NIH, Bethesda, USA., Ovbiagele B; Genetics and Cell Biology Unit, Department of Zoology, Faculty of Science, University of Ibadan, Ibadan, Nigeria., Owolabi MO; Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria. mayowaowolabi@yahoo.com.; Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria. mayowaowolabi@yahoo.com.; University College Hospital, Ibadan, Nigeria. mayowaowolabi@yahoo.com.; Lebanese American University of Beirut, Beirut, Lebanon. mayowaowolabi@yahoo.com.; Blossom Specialist Medical Center, Ibadan, Nigeria. mayowaowolabi@yahoo.com.
Jazyk: angličtina
Zdroj: Genome medicine [Genome Med] 2024 Feb 05; Vol. 16 (1), pp. 25. Date of Electronic Publication: 2024 Feb 05.
DOI: 10.1186/s13073-023-01273-5
Abstrakt: Background: African ancestry populations have the highest burden of stroke worldwide, yet the genetic basis of stroke in these populations is obscure. The Stroke Investigative Research and Educational Network (SIREN) is a multicenter study involving 16 sites in West Africa. We conducted the first-ever genome-wide association study (GWAS) of stroke in indigenous Africans.
Methods: Cases were consecutively recruited consenting adults (aged > 18 years) with neuroimaging-confirmed ischemic stroke. Stroke-free controls were ascertained using a locally validated Questionnaire for Verifying Stroke-Free Status. DNA genotyping with the H3Africa array was performed, and following initial quality control, GWAS datasets were imputed into the NIH Trans-Omics for Precision Medicine (TOPMed) release2 from BioData Catalyst. Furthermore, we performed fine-mapping, trans-ethnic meta-analysis, and in silico functional characterization to identify likely causal variants with a functional interpretation.
Results: We observed genome-wide significant (P-value < 5.0E-8) SNPs associations near AADACL2 and miRNA (MIR5186) genes in chromosome 3 after adjusting for hypertension, diabetes, dyslipidemia, and cardiac status in the base model as covariates. SNPs near the miRNA (MIR4458) gene in chromosome 5 were also associated with stroke (P-value < 1.0E-6). The putative genes near AADACL2, MIR5186, and MIR4458 genes were protective and novel. SNPs associations with stroke in chromosome 2 were more than 77 kb from the closest gene LINC01854 and SNPs in chromosome 7 were more than 116 kb to the closest gene LINC01446 (P-value < 1.0E-6). In addition, we observed SNPs in genes STXBP5-AS1 (chromosome 6), GALTN9 (chromosome 12), FANCA (chromosome 16), and DLGAP1 (chromosome 18) (P-value < 1.0E-6). Both genomic regions near genes AADACL2 and MIR4458 remained significant following fine mapping.
Conclusions: Our findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke's risk prediction and development of new targeted interventions to prevent or treat stroke.
(© 2024. The Author(s).)
Databáze: MEDLINE
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