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Impact of body composition on COVID-19 susceptibility and severity: A two-sample multivariable Mendelian randomization study.

Metabolism 118:154732 (2021)
Verlagsversion Forschungsdaten DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
OBJECTIVES: Recent studies suggested obesity to be a possible risk factor for COVID-19 disease in the wake of the coronavirus (SARS-CoV-2) infection. However, the causality and especially the role of body fat distribution in this context is still unclear. Thus, using a univariable as well as multivariable two-sample Mendelian randomization (MR) approach, we investigated for the first time the causal impact of body composition on the susceptibility and severity of COVID-19. METHODS: As indicators of overall and abdominal obesity we considered the measures body mass index (BMI), waist circumference (WC), and trunk fat ratio (TFR). Summary statistics of genome-wide association studies (GWASs) for these body composition measures were drawn from the GIANT consortium and UK Biobank, while for susceptibility and severity due to COVID-19 disease data from the COVID-19 Host Genetics Initiative was used. For the COVID-19 cohort neither age nor gender was available. Total and direct causal effect estimates were calculated using Single Nucleotide Polymorphisms (SNPs), sensitivity analyses were done applying several robust MR techniques and mediation effects of type 2 diabetes (T2D) and cardiovascular diseases (CVD) were investigated within multivariable MR analyses. RESULTS: Genetically predicted BMI was strongly associated with both, susceptibility (OR = 1.31 per 1 SD increase; 95% CI: 1.15-1.50; P-value = 7.3·10-5) and hospitalization (OR = 1.62 per 1 SD increase; 95% CI: 1.33-1.99; P-value = 2.8·10-6) even after adjustment for genetically predicted visceral obesity traits. These associations were neither mediated substantially by T2D nor by CVD. Finally, total but not direct effects of visceral body fat on outcomes could be detected. CONCLUSIONS: This study provides strong evidence for a causal impact of overall obesity on the susceptibility and severity of COVID-19 disease. The impact of abdominal obesity was weaker and disappeared after adjustment for BMI. Therefore, obese people should be regarded as a high-risk group. Future research is necessary to investigate the underlying mechanisms linking obesity with COVID-19.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Body Composition ; Body Fat Distribution ; Covid-19 ; Mendelian Randomization ; Obesity ; Sars-cov-2; Immune-response; Obesity; Loci; Adipose; Metaanalysis; Association
ISSN (print) / ISBN 0026-0495
e-ISSN 1532-8600
Quellenangaben Band: 118, Heft: , Seiten: , Artikelnummer: 154732 Supplement: ,
Verlag Elsevier
Verlagsort 1600 John F Kennedy Boulevard, Ste 1800, Philadelphia, Pa 19103-2899 Usa
Begutachtungsstatus Peer reviewed