Leveraging genetic data to elucidate the relationship between Covid-19 and ischemic stroke

Autor: Christopher D. Anderson, Dipender Gill, Alan C. Cameron, Leonardo Bottolo, Jesse Dawson, Verena Zuber, Evangelos Pavlos Myserlis, Stephen Burgess, Israel Fernandez-Cadenas
Přispěvatelé: Commission of the European Communities, Zuber, Verena [0000-0001-9827-1877], Cameron, Alan [0000-0001-6965-1109], Myserlis, Evangelos P [0000-0002-7310-624X], Bottolo, Leonardo [0000-0002-6381-2327], Fernandez-Cadenas, Israel [0000-0003-4821-2363], Burgess, Stephen [0000-0001-5365-8760], Anderson, Christopher D [0000-0002-0053-2002], Gill, Dipender [0000-0001-7312-7078], Apollo - University of Cambridge Repository
Rok vydání: 2021
Předmět:
Oncology
Linkage disequilibrium
medicine.medical_specialty
Cardiac & Cardiovascular Systems
Epidemiology
OUTBREAK
Genome-wide association study
Disease
Polymorphism
Single Nucleotide
Article
Body Mass Index
Brain Ischemia
Risk Factors
COVID‐19
Internal medicine
Mendelian randomization
Genetics
ischemic stroke
medicine
Humans
Diseases of the circulatory (Cardiovascular) system
GENOME-WIDE ASSOCIATION
cross‐trait linkage disequilibrium score regression
1102 Cardiorespiratory Medicine and Haematology
Original Research
Genetic association
RISK
Inflammation
Science & Technology
business.industry
Smoking
Confounding
COVID-19
cross-trait linkage disequilibrium score regression
Mendelian Randomization Analysis
Odds ratio
INSTRUMENTS
Confidence interval
C-Reactive Protein
BIAS
RC666-701
Cardiovascular System & Cardiology
Cardiology and Cardiovascular Medicine
business
Life Sciences & Biomedicine
Body mass index
Genome-Wide Association Study
Zdroj: Journal of the American Heart Association
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
medRxiv
article-version (status) pre
article-version (number) 1
ISSN: 2047-9980
Popis: BackgroundThe relationship between coronavirus disease 2019 (Covid-19) and ischemic stroke is poorly defined. We aimed to leverage genetic data to investigate reported associations.MethodsGenetic association estimates for liability to Covid-19 and cardiovascular traits were obtained from large-scale consortia. Analyses primarily focused on critical Covid-19, defined as hospitalization with Covid-19 requiring respiratory support or resulting in death. Cross-trait linkage disequilibrium score regression was used to estimate genetic correlations of critical Covid-19 with ischemic stroke, other related cardiovascular outcomes, and risk factors common to both Covid-19 and cardiovascular disease (body mass index, smoking and chronic inflammation, estimated using C-reactive protein). Mendelian randomization analysis was performed to investigate whether liability to critical Covid-19 was associated with increased risk of any of the cardiovascular outcomes for which genetic correlation was identified.ResultsThere was evidence of genetic correlation between critical Covid-19 and ischemic stroke (rg=0.29, FDRp-value=4.65×10−3), body mass index (rg=0.21, FDR-p-value=6.26×10−6) and C-reactive protein (rg=0.20, FDR-p-value=1.35×10−4), but none of the other considered traits. In Mendelian randomization analysis, liability to critical Covid-19 was associated with increased risk of ischemic stroke (odds ratio [OR] per logOR increase in genetically predicted critical Covid-19 liability 1.03, 95% confidence interval 1.00-1.06,p-value=0.03). Similar estimates were obtained when considering ischemic stroke subtypes. Consistent estimates were also obtained when performing statistical sensitivity analyses more robust to the inclusion of pleiotropic variants, including multivariable Mendelian randomization analyses adjusting for potential genetic confounding through body mass index, smoking and chronic inflammation. There was no evidence to suggest that genetic liability to ischemic stroke increased the risk of critical Covid-19.ConclusionsThese data support that liability to critical Covid-19 is associated with an increased risk of ischemic stroke. The host response predisposing to severe Covid-19 is likely to increase the risk of ischemic stroke, independent of other potentially mitigating risk factors.
Databáze: OpenAIRE
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