Shared genetic background between SARS-CoV-2 infection and large artery stroke.

COVID-19 SARS-CoV-2 cerebrovascular disorders ischaemic stroke large artery stroke stroke

Journal

International journal of stroke : official journal of the International Stroke Society
ISSN: 1747-4949
Titre abrégé: Int J Stroke
Pays: United States
ID NLM: 101274068

Informations de publication

Date de publication:
11 May 2022
Historique:
pubmed: 12 4 2022
medline: 12 4 2022
entrez: 11 4 2022
Statut: aheadofprint

Résumé

Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population. We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection ( Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR = 1.05 per SD increase, 95% CI: (1.00, 1.10), p = 0.04) and MEGASTROKE (β = 0.510, 95% CI: (0.242, 0.779), FDR-p = 0.0019). The SARS-CoV-2 risk-related Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness.

Sections du résumé

BACKGROUND AND AIMS UNASSIGNED
Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population.
PATIENTS AND METHODS UNASSIGNED
We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection (
RESULTS UNASSIGNED
Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR = 1.05 per SD increase, 95% CI: (1.00, 1.10), p = 0.04) and MEGASTROKE (β = 0.510, 95% CI: (0.242, 0.779), FDR-p = 0.0019). The SARS-CoV-2 risk-related
CONCLUSION UNASSIGNED
Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness.

Identifiants

DOI: 10.1177/17474930221095696 PMID: 35403514
pubmed: 35403514
doi: 10.1177/17474930221095696
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

17474930221095696

Auteurs

Livia Parodi (L)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-0605-2381

Evangelos Pavlos Myserlis (EP)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Jaeyoon Chung (J)

Department of Medicine, Boston University School of Medicine, Boston, MA, USA.

Marios K Georgakis (MK)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Ernst Mayerhofer (E)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0001-8902-4209

Jonathan Henry (J)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Bailey E Montgomery (BE)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Mandy Moy (M)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Huichun Xu (H)

University of Maryland School of Medicine, Baltimore, MD, USA.

Rainer Malik (R)

Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany.

Carl D Langefeld (CD)

Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Martin Dichgans (M)

Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany.

Daniel Woo (D)

Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.

Jonathan Rosand (J)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Christopher D Anderson (CD)

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.

Classifications MeSH