key: cord-0787889-0lnlrhg1
authors: Ran, Shu; Zhang, Shuyu; Chen, Huiting; Zhao, Minfei; Liu, Baolin
title: Total body bone mineral density and severe COVID-19: A Mendelian randomization analysis in five age strata
date: 2021-12-01
journal: Bone
DOI: 10.1016/j.bone.2021.116281
sha: 67d9cc79aaa7045dbc4a5305b8bd85f8a873f1fc
doc_id: 787889
cord_uid: 0lnlrhg1

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However, Tahtabasi et al. [3] reported that vertebral BMD and lower BMD were significant independent predictors of COVID-19 mortality in both univariate and multivariate regression analysis but their study included 63 patients of low BMD and the mean age was 72.1 ± 12.6 years. Thus, the main take-home message is whether the prognostic relevance of low BMD as a risk factor for SARS-CoV-2 infected patients persists in a selected age group. In this study, we want to present some information in potential association between total body BMD (TBBMD) stratified by five levels of age and COVID-19, and then discuss the causality.

The causality of the association between BMD and severe COVID-19 has not been established because observational studies are prone to the effects of confounding factors.

Mendelian randomization (MR) exploits genetic variants as instrumental variables to bring down confusion about environmental or other disease factors because alleles are randomly assigned to offspring. In this study, we performed a two-sample MR analysis for the association of TBBMD with severe COVID-19 to validate the authors' findings.

Summary statistics of TBBMD were obtained from the Genetic Factors for Osteoporosis (GEFOS) Consortium [4] . Age strata comprised 0-15 years (N = 11 807), 15- The COVID-19 Host Genetics Initiative genome-wide association meta-analysis (release 6, 15 June, 2021; without the 23andMe study) [5] , which included 8 779 very severe respiratory confirmed COVID-19 cases versus 1 001 875 population controls. The MR analyses were performed using the inverse-variance weighted method, but the multiple-SNP test is not applicable to features that contain only one instrumental variable, in which case we use the Wald ratio test [6] . All summary data used in this work are publicly available. They were obtained with relevant participant consent and ethical approval.

Single-nucleotide polymorphisms (SNPs) at p < 5×10 −8 were selected as instrumental variables. The linkage disequilibrium threshold was set to r 2 = 0.001 within a distance of 10 000 kb. (table 1) . There were no strong evidences supporting associations of COVID-19 with TBBMD in the four different age strata, namely 0-15, 15-30, 30-45, and 45-60 years. Our results showed that potential association between BMD and severe COVID-19 in aged population and revealed that the higher TBBMD is a protective factor for COVID-19 in people over 60 years of age compared to other age groups. It meant that the higher BMD is in people over 60 years of age, the less likely they are to develop more severe COVID-19. We demonstrated that BMD could be a predictor of severe COVID-19 in aged population to identify cases with severe progressions and to predict whether a patient should be treated in an ICU within the observation period. It was confirmed that BMD was eliminated from the multivariate logistic regression of Kottlors et al. [1] primarily due to a high collinearity between age and BMD.

In conclusion, we investigated the impacts of age-stratified TBBMD risk on severe COVID-19 using large-scale genetic summary data. With performing a more homogenous patient age, the potential effects between low BMD and COVID-19 in aged population were illustrated. The findings may help shed light on the clinical implications. BMD can provide guidance for clinical treatment to predict whether infected patients need to be treated in the intensive care unit (ICU), and more attention should be paid to elderly patients with low BMD. Abbreviations: CI, confidence interval; TBBMD, total body bone mineral density; OR, odds ratio; SNP, single-nucleotide polymorphism. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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