School of Systems Biology, George Mason University, Manassas, VA.
Research Centre for Medical Genetics, Moscow, Russia.
Diabetes. 2023 Jan 1;72(1):149-154. doi: 10.2337/db22-0610.
Many coronavirus disease 2019 (COVID-19) risk factors, including obesity and diabetes, are associated with an abnormal basal metabolic rate (BMR). We aimed to evaluate whether BMR could impact the susceptibility to or severity of COVID-19. We performed genetic correlation and Mendelian randomization (MR) analyses to assess genetic correlations and potential causal associations between BMR (n = 448,348) and three COVID-19 outcomes: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and critical COVID-19 (n = 1,086,211-2,597,856). A multivariable MR (MVMR) analysis was used to estimate the direct effect of BMR on COVID-19 independent of BMI and type 2 diabetes. BMR has positive genetic correlations with the COVID-19 outcomes (genetic correlations 0.213-0.266). The MR analyses indicated that genetic liability to BMR confers causal effects on SARS-CoV-2 infection (odds ratio 1.14, 95% CI 1.09-1.20, P = 1.65E-07), hospitalized COVID-19 (1.31, 1.18-1.46, P = 8.69E-07), and critical COVID-19 (1.04, 1.19-1.64, P = 4.89E-05). Sensitivity analysis of MR showed no evidence of directional pleiotropy or heterogeneity, indicating the robustness of its results. The MVMR analysis showed that the causal effects of BMR on hospitalized COVID-19 and critical COVID-19 were dependent on BMI and type 2 diabetes but that BMR may affect the SARS-CoV-2 infection risk independently of BMI and type 2 diabetes (odds ratio 1.09, 95% CI 1.03-1.15, P = 4.82E-03). Our study indicates that a higher BMR contributes to amplifying the susceptibility to and severity of COVID-19. The causal effect of BMR on the severity of COVID-19 may be mediated by BMI and type 2 diabetes.
许多 2019 年冠状病毒病（COVID-19）的风险因素，包括肥胖和糖尿病，都与基础代谢率（BMR）异常有关。我们旨在评估 BMR 是否会影响 COVID-19 的易感性或严重程度。我们进行了遗传相关性和孟德尔随机化（MR）分析，以评估 BMR（n=448348）与三种 COVID-19 结局之间的遗传相关性和潜在因果关系：严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染、COVID-19 住院和重症 COVID-19（n=1086211-2597856）。多变量 MR（MVMR）分析用于估计 BMR 对 COVID-19 的直接影响，独立于 BMI 和 2 型糖尿病。BMR 与 COVID-19 结局呈正遗传相关性（遗传相关性 0.213-0.266）。MR 分析表明，BMR 的遗传易感性对 SARS-CoV-2 感染有因果影响（比值比 1.14，95%CI 1.09-1.20，P=1.65E-07）、住院 COVID-19（1.31，1.18-1.46，P=8.69E-07）和重症 COVID-19（1.04，1.19-1.64，P=4.89E-05）。MR 的敏感性分析没有发现方向性偏倚或异质性的证据，表明其结果具有稳健性。MVMR 分析表明，BMR 对住院 COVID-19 和重症 COVID-19 的因果影响取决于 BMI 和 2 型糖尿病，但 BMR 可能独立于 BMI 和 2 型糖尿病影响 SARS-CoV-2 感染的风险（比值比 1.09，95%CI 1.03-1.15，P=4.82E-03）。我们的研究表明，较高的 BMR 有助于增加 COVID-19 的易感性和严重程度。BMR 对 COVID-19 严重程度的因果影响可能通过 BMI 和 2 型糖尿病介导。
