4 research outputs found
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
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 ancestry(1,2). 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 analysis(3), 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 approach(4), 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 ancestry(5). 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.</p
Enseñar y aprender en época de cambios : XXVI Premios Francisco Giner de los Ríos a la Mejora de la Calidad Educativa
En esta edición de los Premios Giner de los Ríos se ha reconocido con el Premio Especial el trabajo llevado a cabo a lo largo de quince años por el profesorado del área de ciencias, junto a sus alumnos, en el estudio de la calidad de las aguas del río Guadalquivir a su paso por Sevilla. En Educación Infantil se ha premiado una webquest basada en la metodología constructivista que consigue el desarrollo de todas las competencias del alumnado e investiga cómo es la vida en la sabana, tundra-polo, selva y desierto. La primera experiencia premiada en Educación Primaria reconoce el esfuerzo de una comunidad educativa en la elaboración de un largometraje sobre Astronomía. La segunda es la creación y puesta en práctica del programa ELIGe©, que ayuda a los alumnos con TEA a la elección de actividades cotidianas, y a la comprensión y expresión de emociones básicas. En Ciencia y Tecnología, se ha premiado el Proyecto bambú, bosquete con variedades de esta planta para trabajar. En Humanidades y Ciencias Sociales, se ha reconocido el valor de una experiencia que transmite al alumnado la idea de que la lengua es la herramienta que permite proyectar una imagen de lo que somos, queremos y anhelamos. En Otras Materias y Áreas Curriculares se ha galardonado un trabajo cuyo objetivo es la enseñanza al alumnado del trabajo autónomo y el desarrollo de la competencia comunicativa. En la modalidad de Trabajos de Aplicación de Conocimientos en Distintos Ámbitos Personales o Sociales, se ha galardonado un proyecto de Formación Profesional que aborda tres objetivos: la integración curricular del desarrollo de proyectos de empresa y simulaciones de entornos reales de trabajo; el cambio en la dinámica del aula con el uso intensivo de la web 2.0; y el cambio en el rol del alumno, que pasa de receptor a creador de conocimiento.MECDES