TY - JOUR
T1 - Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome
T2 - From Early Brain Injury to Long-Term Recovery
AU - Lee, Jin Moo
AU - Fernandez-Cadenas, Israel
AU - Lindgren, Arne G.
N1 - Publisher Copyright:
© 2021 American Heart Association, Inc.
PY - 2021
Y1 - 2021
N2 - There is a critical need to elucidate molecular mechanisms underlying brain injury, repair, and recovery following ischemic stroke-a global health problem with major social and economic impact. Despite 5 decades of intensive research, there are no widely accepted neuroprotective drugs that mitigate ischemic brain injury, or neuroreparative drugs, or personalized approaches that guide therapies to enhance recovery. 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-including 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-including exploiting informatics, multi-omics, and novel analytics-promise to uncover genetic and molecular pathways from which drug targets and other new interventions may be identified.
AB - There is a critical need to elucidate molecular mechanisms underlying brain injury, repair, and recovery following ischemic stroke-a global health problem with major social and economic impact. Despite 5 decades of intensive research, there are no widely accepted neuroprotective drugs that mitigate ischemic brain injury, or neuroreparative drugs, or personalized approaches that guide therapies to enhance recovery. 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-including 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-including exploiting informatics, multi-omics, and novel analytics-promise to uncover genetic and molecular pathways from which drug targets and other new interventions may be identified.
KW - brain injuries
KW - genetic architecture
KW - genetics
KW - ischemic stroke
KW - outcomes research
KW - phenotypes
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=85113777079&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.121.032622
DO - 10.1161/STROKEAHA.121.032622
M3 - Review article
C2 - 34399587
AN - SCOPUS:85113777079
SP - 3013
EP - 3024
JO - Stroke
JF - Stroke
SN - 0039-2499
ER -