Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke

Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Peer reviewe

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

¿Por qué y para qué sistematizar las experiencias de extensión universitaria?

A Sistematização de Experiências, como proposta para a produção de conhecimento a partir de práticas educacionais, organizacionais e de processos sociais comunitários, tornou-se nos últimos anos um tema de grande interesse em diversas áreas, e com crescente aceitação nas práticas de Extensão Universitária.Achamos nas Universidades uma crescente preocupação com a necessidade de fortalecer a produção e a circulação do conhecimento acadêmico a partir dos projetos, programas e atividades de Extensão ou Ação Social e suas vinculações com as dimensões de ensino e pesquisa.A definição de uma proposta conceitual de Sistematização de Experiências e diretrizes metodológicas que a viabilizem, tem sido colocada em prática em diversos programas de formação e educação, que apresentam novas e importantes possibilidades e desafios.La Sistematización de Experiencias, como propuesta de producción de conocimiento desde las prácticas educativas, organizativas y de procesos sociales comunitarios se ha ido convirtiendo en los últimos años en una temática de mucho interés en diversos ámbitos, y cada vez con mayor acogida en el de las experiencias de Extensión Universitaria.Encontramos en las Universidades una preocupación creciente en torno a la necesidad de fortalecer la producción y circulación de conocimiento académico desde los proyectos, programas y actividades de Extensión o Acción Social y sus vínculos con las dimensiones docente e investigativa.La definición de una propuesta conceptual de Sistematización de Experiencias y pautas metodológicas que la hagan viable, se ha ido poniendo en práctica en diversos programas de formación y capacitación, los cuales nos plantean nuevas e importantes posibilidades y desafíos.The Systematization of Experiences, as a proposal for the production of knowledge from educational, organizational and community social practices, has become in recent years a topic of great interest in various fields, and with increasing acceptance in the field of the University Extension (Community, Social Action) experiences.We find at the Universities a growing concern about the need to strengthen the production and circulation of academic knowledge from the projects, programs and activities of Extension or Social Action and its links with teaching and research dimensions.The definition of a conceptual proposition of Systematization of Experiences and methodological guidelines that make it viable, has been put into practice in various training and education programs, which pose new and important possibilities and challenges

Monitor educador

Los educadores populares tenemos la exigencia de organizar y conducir procesos en los que la gente produzca, construya procesos de nuevos conocimientos. Procesos en los que se genere la capacidad de conceptualizar y no sólo se aprendan conceptos. Los procesos de educación popular enfrentan el reto de continuar siendo factores de dinamización para la gestión y construcción de alternativas, tanto en el terreno de la elaboración teórica y la respuesta práctica, como en la afirmación ética.MadridES

¿Por qué y para qué sistematizar las experiencias de extensión universitaria?

La Sistematización de Experiencias, como propuesta de producción de conocimiento desde las prácticas educativas, organizativas y de procesos sociales comunitarios se ha ido convirtiendo en los últimos años en una temática de mucho interés en diversos ámbitos, y cada vez con mayor acogida en el de las experiencias de Extensión Universitaria.Encontramos en las Universidades una preocupación creciente en torno a la necesidad de fortalecer la producción y circulación de conocimiento académico desde los proyectos, programas y actividades de Extensión o Acción Social y sus vínculos con las dimensiones docente e investigativa.La definición de una propuesta conceptual de Sistematización de Experiencias y pautas metodológicas que la hagan viable, se ha ido poniendo en práctica en diversos programas de formación y capacitación, los cuales nos plantean nuevas e importantes posibilidades y desafíos.A Sistematização de Experiências, como proposta para a produção de conhecimento a partir de práticas educacionais, organizacionais e de processos sociais comunitários, tornou-se nos últimos anos um tema de grande interesse em diversas áreas, e com crescente aceitação nas práticas de Extensão Universitária.Achamos nas Universidades uma crescente preocupação com a necessidade de fortalecer a produção e a circulação do conhecimento acadêmico a partir dos projetos, programas e atividades de Extensão ou Ação Social e suas vinculações com as dimensões de ensino e pesquisa.A definição de uma proposta conceitual de Sistematização de Experiências e diretrizes metodológicas que a viabilizem, tem sido colocada em prática em diversos programas de formação e educação, que apresentam novas e importantes possibilidades e desafios.The Systematization of Experiences, as a proposal for the production of knowledge from educational, organizational and community social practices, has become in recent years a topic of great interest in various fields, and with increasing acceptance in the field of the University Extension (Community, Social Action) experiences.We find at the Universities a growing concern about the need to strengthen the production and circulation of academic knowledge from the projects, programs and activities of Extension or Social Action and its links with teaching and research dimensions.The definition of a conceptual proposition of Systematization of Experiences and methodological guidelines that make it viable, has been put into practice in various training and education programs, which pose new and important possibilities and challenges

Comunicación Popular y Movimientos Sociales en Centroamérica.

Ponencia48p

Monitor educador

Entrevista a Oscar Jara, coordinador de 'Alforja', red de educación popular centroamericana, sobre la situación de los países pobres y las medidas que se pueden tomar.MadridES

100 Cartas para Paulo Freire de quienes pretendemos Enseñar

Realizar un texto colectivo como “100 Cartas para Paule Freire de quienes pretendemos Enseñar”, es un desafío al reunir el aprehender desde el sentido profesional de la educación y con el espíritu de transformación, desde la educación como un espacio endógeno de revolución y exógeno a las comunidades y sociedades, en busca de un sentido de identidad. Hoy desde una crítica decolonial, antirracista, feminista y ecologica en la construcción de un sentido real que busque enfrentar el sistema hegemónico y destructivo que se ha impuesto con explotación, sangre y libertades de nuestro pueblo