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We here explore novel reverse translational approaches that will complement traditional forward translational methods in identifying mechanisms relevant to human stroke outcome. Although genome-wide association studies have yielded over 30 genetic loci that influence ischemic stroke risk, only a few genome-wide association studies have been performed for stroke outcome. We discuss important considerations for genetic studies of ischemic stroke outcome\u2014including carefully designed phenotypes that capture injury\/recovery mechanisms, anchored in time to stroke onset. We also address recent genome-wide association studies that provide insight into mechanisms underlying brain injury and repair. There are several ongoing initiatives exploring genomic associations with novel phenotypes related to stroke outcome. To improve the understanding of the genetic architecture of ischemic stroke outcome, larger studies using standardized phenotypes, preferably embedded in standard-of-care measures, are needed. Novel techniques beyond genome-wide association studies\u2014including exploiting informatics, multi-omics, and novel analytics\u2014promise to uncover genetic and molecular pathways from which drug targets and other new interventions may be identified.<\/jats:p>","DOI":"10.1161\/strokeaha.121.032622","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T05:00:29Z","timestamp":1629176429000},"page":"3013-3024","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome: From Early Brain Injury to Long-Term Recovery"],"prefix":"10.1161","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-0906","authenticated-orcid":true,"given":"Jin-Moo","family":"Lee","sequence":"first","affiliation":[{"name":"The Hope Center for Neurological Disorders, Department of Neurology, Washington University School of Medicine, St. Louis, MO (J.-M.L)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Fernandez-Cadenas","sequence":"additional","affiliation":[{"name":"Stroke Pharmacogenomics and Genetics Group, Sant Pau Biomedical Research Institute, Barcelona, Spain (I.F.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1942-7330","authenticated-orcid":true,"given":"Arne G.","family":"Lindgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Neurology, Lund University, Sweden (A.G.L.)."},{"name":"Department of Neurology, Sk\u00e5ne University Hospital, Lund, Sweden (A.G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2019.01522"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0058-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/2020.10.29.20222257"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007138"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313533"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.023097"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.029606"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000506396"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649503"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930211007288"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17722095"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00114-9"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.594672"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2018.10.013"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13077"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-020-00396-7"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12984-016-0148-3"},{"key":"e_1_3_3_19_2","first-page":"298","article-title":"Angiogenesis, neurogenesis and brain recovery of function following injury.","volume":"11","author":"Xiong Y","year":"2010","unstructured":"Xiong, Y, Mahmood, A, Chopp, M. 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