Shared genomic architecture between COVID-19 severity and numerous clinical and physiologic parameters revealed by LD score regression analysis

• Published in: Scientific reports 2022-02, Vol.12 (1), p.1891-1891, Article 1891
• Main Authors: Byun, Jinyoung, Han, Younghun, Walsh, Kyle M., Park, Amy S., Bondy, Melissa L., Amos, Christopher I.
• Format: Article
• Language: English
• Subjects: 631/208/205/2138; 631/208/727/2000; Apolipoprotein A; Asymptomatic infection; Biomarkers; Body Mass Index; Coronaviruses; COVID-19; COVID-19 - etiology; COVID-19 - genetics; Diabetes mellitus; Diabetes Mellitus - genetics; Dyspnea - genetics; Epidemiology; Female; Genetic analysis; Genome-Wide Association Study; Genomics; High density lipoprotein; Humanities and Social Sciences; Humans; Linkage disequilibrium; Linkage Disequilibrium - genetics; Male; Mendelian Randomization Analysis; multidisciplinary; Multifactorial Inheritance; Nutrients; Pandemics; Patient Acuity; Phenotype; Phenotypes; Polygenic inheritance; Regression Analysis; Risk Factors; Science; Science (multidisciplinary); Sensitivity analysis; Smoking; Smoking - genetics; Therapeutic targets; Vitamin A; Vitamin D; Vitamin E
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-05832-5

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.