Genetic Associations With Plasma Angiotensin Converting Enzyme 2 Concentration

Male sex has emerged as a major independent risk factor for severe disease and death from severe acute respiratory syndrome coronavirus (SARS-CoV-2) related coronavirus disease 2019 (COVID-19). SARS-COV-2 infects cells via the angiotensin converting enzyme 2 (ACE2) receptor, a widely distributed cell-surface receptor. In two cohorts of patients with heart failure (BIOSTAT), we recently showed that age-adjusted plasma concentrations of ACE2 are higher in men compared with women. To explore whether there are sex-specific genotype effects on plasma ACE2 concentrations we undertook sex-specific and combined genome-wide associations studies of plasma ACE2, measured using the Olink platform (which provides results expressed in the form of relative quantification without units), in the combined index and validation cohorts of BIOSTAT (2420 men and 1022 women, mean age 70.9±11.6 years).