Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome : From Early Brain Injury to Long-Term Recovery
(2021) In Stroke 52(9). p.3013-3024- Abstract
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... (More)
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.
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- author
- Lee, Jin Moo ; Fernandez-Cadenas, Israel and Lindgren, Arne G. LU
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- brain injuries, genetic architecture, genetics, ischemic stroke, outcomes research, phenotypes, prognosis
- in
- Stroke
- volume
- 52
- issue
- 9
- pages
- 12 pages
- publisher
- American Heart Association
- external identifiers
-
- pmid:34399587
- scopus:85113777079
- ISSN
- 0039-2499
- DOI
- 10.1161/STROKEAHA.121.032622
- language
- English
- LU publication?
- no
- id
- e368da67-f253-4a4c-839b-7fe4539b46c6
- date added to LUP
- 2021-09-28 16:19:50
- date last changed
- 2024-06-15 17:00:14
@article{e368da67-f253-4a4c-839b-7fe4539b46c6,
abstract = {{<p>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.</p>}},
author = {{Lee, Jin Moo and Fernandez-Cadenas, Israel and Lindgren, Arne G.}},
issn = {{0039-2499}},
keywords = {{brain injuries; genetic architecture; genetics; ischemic stroke; outcomes research; phenotypes; prognosis}},
language = {{eng}},
number = {{9}},
pages = {{3013--3024}},
publisher = {{American Heart Association}},
series = {{Stroke}},
title = {{Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome : From Early Brain Injury to Long-Term Recovery}},
url = {{http://dx.doi.org/10.1161/STROKEAHA.121.032622}},
doi = {{10.1161/STROKEAHA.121.032622}},
volume = {{52}},
year = {{2021}},
}