Acute Endophenotypes Working Group

Chair / Co-Chairs:Jin-Moo Lee and Israel Fernández-Cadenas


The Acute endophenotypes working group aims to use human genomics and other mutli-omic approaches to elucidate mechanisms involved in early brain injury following acute stroke. Studies exploit creative phenotypes or quantitative endophenotypes that capture different mechanisms involved in acute ischemic stroke. This working group, made up of over 20 investigators representing 14 institutions throughout the world, pursues a variety of projects.


Examples of projects include:  1) the Genetics of Early Instability after Ischemic Stroke (GENISIS); 2) Genetics of hemorrhagic transformation after thrombolysis/thrombectomy; 3) Genetics of edema formation following acute ischemic stroke; among many others. The working group perform different approaches to study these end-points, such as Genome Wide Association studies (GWAs), Exome sequencing, Epigenome Wide Association studies (EWAs) or Transcriptomics. The GENISIS study has analysed samples from 6,000 acute ischemic stroke patients, looking for genetic associations with early neurological improvement or deterioration within the first 24h after stroke. Seven genome-wide associated loci have been found, including several involved in neuroprotective mechanisms. Other projects are the Geno-tPA or TOTO studies focused on pharmacogenetics of rt-PA. In the case of Geno-tPA 1.200 patients have been analysed using GWAs, revealing one locus associated with haemorrhagic transformation after rt-PA. 


In collaboration with the Stroke Outcomes Working Group, the Acute Endophenotypes Working Group has established the ISGC Global Alliance for Acute and Long-Term Outcome Studies.  This Alliance has created common data elements to capture both acute and long-term phenotypes to be obtained in “big data” natural history studies of acute stroke. The hope is to coordinate data collection across multiple large genomic studies in order to expand available data.