Kolawole Wasiu Wahab1, Hemant K Tiwari2, Bruce Ovbiagele3, Fred Sarfo4, Rufus Akinyemi5, Matthew Traylor6, Charles Rotimi7, Hugh Stephen Markus6, Mayowa Owolabi8. 1. Department of Medicine, College of Health Sciences, University of Ilorin, Ilorin, Nigeria. 2. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, USA. 3. Department of Neurology, University of California, San Francisco, USA. 4. Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. 5. Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria; Department of Medicine, University of Ibadan, Ibadan, Nigeria. 6. University of Cambridge, Cambridge, UK. 7. Center for Research on Genomics and Global Health, NHGRI, NIH, Bethesda, MD, USA. 8. Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria; Department of Medicine, University of Ibadan, Ibadan, Nigeria. Electronic address: mayowaowolabi@yahoo.com.
Abstract
BACKGROUND: Although highly heritable, few genes have been linked to spontaneous intracerebral hemorrhage (SICH), which does not currently have any evidence-based disease-modifying therapy. Individuals of African ancestry are especially susceptible to SICH, even more so for indigenous Africans. We systematically reviewed the genetic variants associated with SICH and examined opportunities for rapidly advancing SICH genomic research for precision medicine. METHOD: We searched the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Genome Wide Association Study (GWAS) catalog and PubMed for original research articles on genetic variants associated with SICH as of 15 June 2019 using the PRISMA guideline. RESULTS: Eight hundred and sixty-four articles were identified using pre-specified search criteria, of which 64 met the study inclusion criteria. Among eligible articles, only 9 utilized GWAS approach while the rest were candidate gene studies. Thirty-eight genetic loci were found to be variously associated with the risk of SICH, hematoma volume, functional outcome and mortality, out of which 8 were from GWAS including APOE, CR1, KCNK17, 1q22, CETP, STYK1, COL4A2 and 17p12. None of the studies included indigenous Africans. CONCLUSION: Given this limited information on the genetic contributors to SICH, more genomic studies are needed to provide additional insights into the pathophysiology of SICH, and develop targeted preventive and therapeutic strategies. This call for additional investigation of the pathogenesis of SICH is likely to yield more discoveries in the unexplored indigenous African populations which also have a greater predilection.
BACKGROUND: Although highly heritable, few genes have been linked to spontaneous intracerebral hemorrhage (SICH), which does not currently have any evidence-based disease-modifying therapy. Individuals of African ancestry are especially susceptible to SICH, even more so for indigenous Africans. We systematically reviewed the genetic variants associated with SICH and examined opportunities for rapidly advancing SICH genomic research for precision medicine. METHOD: We searched the National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Genome Wide Association Study (GWAS) catalog and PubMed for original research articles on genetic variants associated with SICH as of 15 June 2019 using the PRISMA guideline. RESULTS: Eight hundred and sixty-four articles were identified using pre-specified search criteria, of which 64 met the study inclusion criteria. Among eligible articles, only 9 utilized GWAS approach while the rest were candidate gene studies. Thirty-eight genetic loci were found to be variously associated with the risk of SICH, hematoma volume, functional outcome and mortality, out of which 8 were from GWAS including APOE, CR1, KCNK17, 1q22, CETP, STYK1, COL4A2 and 17p12. None of the studies included indigenous Africans. CONCLUSION: Given this limited information on the genetic contributors to SICH, more genomic studies are needed to provide additional insights into the pathophysiology of SICH, and develop targeted preventive and therapeutic strategies. This call for additional investigation of the pathogenesis of SICH is likely to yield more discoveries in the unexplored indigenous African populations which also have a greater predilection.
Authors: Daniel Woo; Jonathan Rosand; Chelsea Kidwell; Jacob L McCauley; Jennifer Osborne; Mark W Brown; Sandra E West; Eric W Rademacher; Salina Waddy; Jamie N Roberts; Sebastian Koch; Nicole R Gonzales; Gene Sung; Steven J Kittner; Lee Birnbaum; Michael Frankel; Fernando Daniel Testai; Christiana E Hall; Mitchell S V Elkind; Matthew Flaherty; Bruce Coull; Ji Y Chong; Tanya Warwick; Marc Malkoff; Michael L James; Latisha K Ali; Bradford B Worrall; Floyd Jones; Tiffany Watson; Anne Leonard; Rebecca Martinez; Ralph I Sacco; Carl D Langefeld Journal: Stroke Date: 2013-09-10 Impact factor: 7.914
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Authors: R O Akinyemi; B Ovbiagele; A Akpalu; C Jenkins; K Sagoe; L Owolabi; F Sarfo; R Obiako; M Gebreziabher; E Melikam; S Warth; O Arulogun; D Lackland; A Ogunniyi; H Tiwari; R N Kalaria; D Arnett; M O Owolabi Journal: Cardiovasc J Afr Date: 2015 Mar-Apr Impact factor: 1.167
Authors: Jingjing Liang; Thu H Le; Digna R Velez Edwards; Bamidele O Tayo; Kyle J Gaulton; Jennifer A Smith; Yingchang Lu; Richard A Jensen; Guanjie Chen; Lisa R Yanek; Karen Schwander; Salman M Tajuddin; Tamar Sofer; Wonji Kim; James Kayima; Colin A McKenzie; Ervin Fox; Michael A Nalls; J Hunter Young; Yan V Sun; Jacqueline M Lane; Sylvia Cechova; Jie Zhou; Hua Tang; Myriam Fornage; Solomon K Musani; Heming Wang; Juyoung Lee; Adebowale Adeyemo; Albert W Dreisbach; Terrence Forrester; Pei-Lun Chu; Anne Cappola; Michele K Evans; Alanna C Morrison; Lisa W Martin; Kerri L Wiggins; Qin Hui; Wei Zhao; Rebecca D Jackson; Erin B Ware; Jessica D Faul; Alex P Reiner; Michael Bray; Joshua C Denny; Thomas H Mosley; Walter Palmas; Xiuqing Guo; George J Papanicolaou; Alan D Penman; Joseph F Polak; Kenneth Rice; Ken D Taylor; Eric Boerwinkle; Erwin P Bottinger; Kiang Liu; Neil Risch; Steven C Hunt; Charles Kooperberg; Alan B Zonderman; Cathy C Laurie; Diane M Becker; Jianwen Cai; Ruth J F Loos; Bruce M Psaty; David R Weir; Sharon L R Kardia; Donna K Arnett; Sungho Won; Todd L Edwards; Susan Redline; Richard S Cooper; D C Rao; Jerome I Rotter; Charles Rotimi; Daniel Levy; Aravinda Chakravarti; Xiaofeng Zhu; Nora Franceschini Journal: PLoS Genet Date: 2017-05-12 Impact factor: 6.020