The COVID-19 pandemic has produced broad clinical manifestations, from asymptomatic infection to hospitalization and death. Despite progress from genomic and clinical epidemiology research, risk factors for developing severe COVID-19 are incompletely understood and identification of modifiable risk factors is desperately needed. We conducted linkage disequilibrium score regression (LDSR) analysis to estimate cross-trait genetic correlation between COVID-19 severity and various polygenic phenotypes. To attenuate the genetic contribution of smoking and BMI, we further conducted sensitivity analyses by pruning genomic regions associated with smoking/BMI and repeating LDSR analyses. We identified robust positive associations between the genetic architecture of severe COVID-19 and both BMI and smoking. We observed strong positive genetic correlation (rg) with diabetes (rg = 0.25) and shortness of breath walking on level ground (rg = 0.28) and novel protective associations with vitamin E (rg = − 0.53), calcium (rg = − 0.33), retinol (rg = − 0.59), Apolipoprotein A (rg = − 0.13), and HDL (rg = − 0.17), but no association with vitamin D (rg = − 0.02). Removing genomic regions associated with smoking and BMI generally attenuated the associations, but the associations with nutrient biomarkers persisted. This study provides a comprehensive assessment of the shared genetic architecture of COVID-19 severity and numerous clinical/physiologic parameters. Associations with blood and plasma-derived traits identified biomarkers for Mendelian randomization studies to explore causality and nominates therapeutic targets for clinical evaluation.
【저자키워드】 Genome-wide association studies, Genetic predisposition to disease, 【초록키워드】 Biomarker, severe COVID-19, Hospitalization, Epidemiology, COVID-19 pandemic, Genetic, COVID-19 severity, smoking, risk factor, clinical manifestations, clinical evaluation, Research, asymptomatic infection, death, BMI, correlation, retinol, genomic, parameters, Blood, Protective, association, HDL, Analysis, Linkage disequilibrium, therapeutic target, Shortness of breath, Phenotypes, genomic region, positive, genetic architecture, robust, produced, conducted, provide, analyses, diabete, associations, attenuate, Apolipoprotein A, Mendelian randomization study, Removing, sensitivity analysis, 【제목키워드】 COVID-19 severity, genomic, regression analysis, parameter,