Association of obesity and its genetic predisposition with the risk of severe COVID-19: Analysis of population-based cohort data

Abstract

Objective: We aimed to examine the associations of obesity-related traits (body mass index [BMI], central obesity) and their genetic predisposition with the risk of developing severe COVID-19 in a population-based data.

Research design and methods: We analyzed data from 489,769 adults enrolled in the UK Biobank-a population-based cohort study. The exposures of interest are BMI categories and central obesity (e.g., larger waist circumference). Using genome-wide genotyping data, we also computed polygenic risk scores (PRSs) that represent an individual's overall genetic risk for each obesity trait. The outcome was severe COVID-19, defined by hospitalization for laboratory-confirmed COVID-19.

Results: Of 489,769 individuals, 33% were normal weight (BMI, 18.5-24.9 kg/m²), 43% overweight (25.0-29.9 kg/m²), and 24% obese (≥30.0 kg/m²). The UK Biobank identified 641 patients with severe COVID-19. Compared to adults with normal weight, those with a higher BMI had a dose-response increases in the risk of severe COVID-19, with the following adjusted ORs: for 25.0-29.9 kg/m², 1.40 (95%CI 1.14-1.73; P = 0.002); for 30.0-34.9 kg/m², 1.73 (95%CI 1.36-2.20; P < 0.001); for 35.0-39.9 kg/m², 2.82 (95%CI 2.08-3.83; P < 0.001); and for ≥40.0 kg/m², 3.30 (95%CI 2.17-5.03; P < 0.001). Likewise, central obesity was associated with significantly higher risk of severe COVID-19 (P < 0.001). Furthermore, larger PRS for BMI was associated with higher risk of outcome (adjusted OR per BMI PRS Z-score 1.14, 95%CI 1.05-1.24; P = 0.004).

Conclusions: In this large population-based cohort, individuals with more-severe obesity, central obesity, or genetic predisposition for obesity are at higher risk of developing severe-COVID-19.

Keywords: Body mass index; COVID-19; Central obesity; Diabetes; GWAS; Hospitalization; Obesity; Polygenic risk score; SARS-CoV-2; UK Biobank.