A cross-species approach using an in vivo evaluation platform in mice demonstrates that sequence variation in human RABEP2 modulates ischemic stroke outcomes

Bogousslavsky, 2003, Stroke: time for a global campaign?, Cerebrovasc. Dis., 16, 111, 10.1159/000070589 Johnson, 2016, Stroke: a global response is needed, Bull. World Health Organ., 94, 10.2471/BLT.16.181636 Krishnamurthi, 2013, Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010, Lancet. Glob. Health, 1, e259, 10.1016/S2214-109X(13)70089-5 Kim, 2020, Global Stroke Statistics 2019, Int. J. Stroke, 15, 819, 10.1177/1747493020909545 Benjamin, 2016, Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association, Circulation, 133 Roger, 2012, Heart disease and stroke statistics-2012 update: a report from the American Heart Association, Circulation, 125 Benjamin, 2019, Heart disease and stroke statistics-2019 update: a report from the American heart association, Circulation, 139, 10.1161/CIR.0000000000000659 Virani, 2020, Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association, Circulation, 141, 10.1161/CIR.0000000000000757 Goyal, 2015, Randomized assessment of rapid endovascular treatment of ischemic stroke, N. Engl. J. Med., 372, 1019, 10.1056/NEJMoa1414905 Kim, 2015, Time-dependent Thrombus resolution after tissue-type plasminogen activator in patients with stroke and mice, Stroke, 46, 1877, 10.1161/STROKEAHA.114.008247 Muchada, 2014, Impact of time to treatment on tissue-type plasminogen activator-induced recanalization in acute ischemic stroke, Stroke, 45, 2734, 10.1161/STROKEAHA.114.006222 Emberson, 2014, Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischemic stroke: a meta-analysis of individual patient data from randomized trials, Lancet, 384, 1929, 10.1016/S0140-6736(14)60584-5 Albers, 2011, STAIR VII Consortium. Stroke Treatment Academic Industry Roundtable (STAIR) recommendations for maximizing the use of intravenous thrombolytics and expanding treatment options with intra-arterial and neuroprotective therapies, Stroke, 42, 2645, 10.1161/STROKEAHA.111.618850 O'Donnell, 2010, Risk factors for ischemic and intracerebral hemorrhagic stroke in 22 countries (the interstroke study): A case-control study, Lancet, 376, 112, 10.1016/S0140-6736(10)60834-3 Go, 2013, Heart disease and stroke statistics-2013 update: A report from the American heart association, Circulation, 127 Elkind, 2007, Why now? Moving from stroke risk factors to stroke triggers, Curr. Opin. Neurol., 20, 51, 10.1097/WCO.0b013e328012da75 Boehme, 2017, Stroke Risk Factors, Genetics, and Prevention, Circ. Res., 120, 472, 10.1161/CIRCRESAHA.116.308398 Gretarsdottir, 2003, The gene encoding phosphodiesterase 4D confers risk of ischemic stroke, Nat. Genet., 35, 131, 10.1038/ng1245 Helgadottir, 2004, The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke, Nat. Genet., 36, 233, 10.1038/ng1311 Matarín, 2007, A genome-wide genotyping study in patients with ischemic stroke: initial analysis and data release, Lancet Neurol., 6, 414, 10.1016/S1474-4422(07)70081-9 Matarin, 2008, Whole genome analyses suggest ischemic stroke and heart disease share an association with polymorphisms on chromosome 9p21, Stroke, 39, 1586, 10.1161/STROKEAHA.107.502963 Matarin, 2008, Structural genomic variation in ischemic stroke, Neurogenetics, 9, 101, 10.1007/s10048-008-0119-3 Keum, 2009, A locus mapping to mouse chromosome 7 determines infarct volume in a mouse model of ischemic stroke, Circ. Cardiovasc. Genet., 2, 591, 10.1161/CIRCGENETICS.109.883231 Keum, 2013, Natural genetic variation of integrin alpha L (Itgal) modulates ischemic brain injury in stroke, PLoS Genet., 9, e1003807, 10.1371/journal.pgen.1003807 Chu, 2013, A novel genetic locus modulates infarct volume independently of the extent of collateral circulation, Physiol. Genomics, 45, 751, 10.1152/physiolgenomics.00063.2013 Lee, 2016, Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume, J. Clin. Invest., 126, 2827, 10.1172/JCI84491 Lee, 2018, Neuronal IL-4Rα modulates neuronal apoptosis and cell viability during the acute phases of cerebral ischemia, FEBS J., 285, 2785, 10.1111/febs.14498 Lee, 2019, Novel neuroprotective loci modulating ischemic stroke volume in wild-derived inbred mouse strains, Genetics, 213, 1079, 10.1534/genetics.119.302555 Lee, 2021, A neuroprotective locus modulates ischemic stroke infarction independent of collateral vessel anatomy, Front. Neurosci., 15, 705160, 10.3389/fnins.2021.705160 Wang, 2012, Genetic Dissection of the Canq1 Locus Governing Variation in Extent of the Collateral Circulation, PLoS One, 7, e31910, 10.1371/journal.pone.0031910 Zhang, 2010, Wide genetic variation in the native pial collateral circulation is a major determinant of variation in severity of stroke, J. Cereb. Blood Flow Metab., 30, 923, 10.1038/jcbfm.2010.10 Lucitti, 2016, Variants of Rab GTPase-Effector Binding Protein-2 Cause Variation in the Collateral Circulation and Severity of Stroke, Stroke, 47, 3022, 10.1161/STROKEAHA.116.014160 Kofler, 2018, The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling, J. Biol. Chem., 293, 4805, 10.1074/jbc.M117.812172 Zhu, 2004, Structural basis of Rab5-Rabaptin5 interaction in endocytosis, Nat. Struct. Mol. Biol., 11, 975, 10.1038/nsmb832 Jumper, 2021, Highly accurate protein structure prediction with AlphaFold, Nature, 596, 583, 10.1038/s41586-021-03819-2 Varadi, 2021, AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models, Nucleic Acids Res., 50, D439, 10.1093/nar/gkab1061 Yan, 2020, The HDOCK server for integrated protein–protein docking, Nat. Protoc., 15, 1829, 10.1038/s41596-020-0312-x Gournier, 1998, Two distinct effectors of the small GTPase Rab5 cooperate in endocytic membrane fusion, EMBO J., 17, 1930, 10.1093/emboj/17.7.1930 Hodge, 2019, Conserved cell types with divergent features in human versus mouse cortex, Nature, 573, 61, 10.1038/s41586-019-1506-7 O'Collins, 2006, 1, 026 experimental treatments in acute stroke, Ann. Neurol., 59, 467, 10.1002/ana.20741 Ginsberg, 2008, Neuroprotection for ischemic stroke: past, present and future, Neuropharmacology, 55, 363, 10.1016/j.neuropharm.2007.12.007 Plenge, 2013, Validating therapeutic targets through human genetics, Nat. Rev. Drug Discov., 12, 581, 10.1038/nrd4051 Nelson, 2015, The support of human genetic evidence for approved drug indications, Nat. Genet., 47, 856, 10.1038/ng.3314 King, 2019, Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval, PLoS Genet., 15, e1008489, 10.1371/journal.pgen.1008489 Turcot, 2018, Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity, Nat. Genet., 50, 26, 10.1038/s41588-017-0011-x Christakoudi, 2021, GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer, Sci. Rep., 11, 10688, 10.1038/s41598-021-89176-6 Vujkovic, 2020, Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis, Nat. Genet., 52, 680, 10.1038/s41588-020-0637-y Berndt, 2013, Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture, Nat. Genet., 45, 501, 10.1038/ng.2606 Grasby, 2020, The genetic architecture of the human cerebral cortex, Science, 367, eaay6690, 10.1126/science.aay6690 Nalls, 2019, Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies, Lancet Neurol., 18, 1091, 10.1016/S1474-4422(19)30320-5 Hill, 2019, A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence, Mol. Psychiatry, 24, 169, 10.1038/s41380-017-0001-5