Individuals with features of metabolic syndrome are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus associated with the severe respiratory disease, coronavirus disease 2019 (COVID-19). Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10 mg/dl increase in serum HDL-cholesterol or apolipoprotein A1 levels was associated with ~10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL-cholesterol revealed that individuals homozygous for apolipoprotein E4 alleles had ~2- to 3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared with apolipoprotein E3 homozygotes, even after adjustment for HDL-cholesterol levels. However, cumulative effects of all evaluated HDL-cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL-cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL-cholesterol and apolipoprotein A1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL-cholesterol levels are associated with SAR-CoV-2 infection.
Sex-specific Genetic Determinants of Cardiometabolic Traits
Although cardiovascular disease (CVD) has traditionally been viewed as a disease of men, new evidence suggests the existence of distinct differences in the risk factors, development, and outcomes between the two sexes. For example, our recent studies have revealed that the genetic factors for several intermediate cardiometabolic traits, such as blood levels of certain amino acids (i.e. glycine) and lipids (i.e. ceramides), represent potentially novel sex-specific mechanisms for CVD. This project proposes to build on our observations using genetic and clinical cardiometabolic data from the UK Biobank. By helping to determine the genetic basis of CVD, our proposed analyses could identify novel therapeutic targets and/or risk stratification tools. Thus, these studies would be consistent with UK Biobank's stated purpose to improve the prevention, diagnosis and treatment of a wide range of illnesses, including heart diseases. The genotype and specific clinical data we request from all UK Biobank participants will be used for statistical analyses. These large-scale computations will specifically test for genetic associations in men and women separately. We will also carry out these sex-stratified tests with the genetic risk factors all combined together in what is typically referred to as `genetic risk score analysis.` Full cohort for genotypes and clinical binary and quantitative CVD traits.
|Lead investigator:||Professor Hooman Allayee|
|Lead institution:||University of Southern California|
2 related Returns
|Return ID||App ID||Description||Archive Date|
|3428||33307||Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma||20 May 2021|
|3431||33307||Genome-wide analysis identifies novel susceptibility loci for myocardial infarction||21 May 2021|