Cardiometabolic risk factors for COVID-19 susceptibility and severity: A Mendelian randomization analysis.
PLoS Med
; 18(3): e1003553, 2021 03.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1117467
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ABSTRACT
BACKGROUND:
Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses. METHODS ANDFINDINGS:
We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10-8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10-5; UK Biobank odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10-5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null.CONCLUSIONS:
In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de la Arteria Coronaria
/
Índice de Masa Corporal
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Accidente Cerebrovascular
/
Diabetes Mellitus Tipo 2
/
Susceptibilidad a Enfermedades
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Insuficiencia Renal Crónica
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COVID-19
/
Obesidad
Tipo de estudio:
Estudio de cohorte
/
Estudios diagnósticos
/
Estudio experimental
/
Estudio observacional
/
Estudio pronóstico
/
Ensayo controlado aleatorizado
/
Revisiones
Tópicos:
Variantes
Límite:
Humanos
Idioma:
Inglés
Revista:
PLoS Med
Asunto de la revista:
Medicina
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
Journal.pmed.1003553
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