Identifying shared genetic loci between coronavirus disease 2019 and cardiovascular diseases based on cross-trait meta-analysis.

People with coronavirus disease 2019 (COVID-19) have different mortality or severity, and this clinical outcome is thought to be mainly attributed to comorbid cardiovascular diseases. However, genetic loci jointly influencing COVID-19 and cardiovascular disorders remain largely unknown. To identify shared genetic loci between COVID-19 and cardiac traits, we conducted a genome-wide cross-trait meta-analysis. Firstly, from eight cardiovascular disorders, we found positive genetic correlations between COVID-19 and coronary artery disease (CAD, R g = 0.4075, P = 0.0031), type 2 diabetes (T2D, R g = 0.2320, P = 0.0043), obesity (OBE, R g = 0.3451, P = 0.0061), as well as hypertension (HTN, R g = 0.233, P = 0.0026). Secondly, we detected 10 shared genetic loci between COVID-19 and CAD, 3 loci between COVID-19 and T2D, 5 loci between COVID-19 and OBE, and 21 loci between COVID-19 and HTN, respectively. These shared genetic loci were enriched in signaling pathways and secretion pathways. In addition, Mendelian randomization analysis revealed significant causal effect of COVID-19 on CAD, OBE and HTN. Our results have revealed the genetic architecture shared by COVID-19 and CVD, and will help to shed light on the molecular mechanisms underlying the associations between COVID-19 and cardiac traits.

up to 2,244 European ancestry critical COVID-19 cases, 60,801 European or uknown ancestry CAD cases, up to 128,820 European or unknown ancestry controls