B1265
Title: Genetic associations from the COVID-19 Host Genetics Initiative highlight biology behind severity and susceptibility
Authors: Andrea Ganna - Institute for Molecular Medicine, Finland (Finland) [presenting]
Abstract: The COVID-19 Host Genetics Initiative (HGI) brings together the international human genetics community to generate, share, and analyze data to identify the genetic determinants of COVID-19 susceptibility and severity. The HGI's 6th data freeze (spring 2021) consists of 61 studies from 24 countries, including ancestries typically underrepresented in genetic studies. The meta-analysis includes 25,027 hospitalized cases and 125,548 cases with lab-confirmed or self-reported PCR-confirmed infection. We find additional genetic variation associated with severe COVID-19 symptoms. Rs35705950 at MUC5B, a strong risk variant for idiopathic pulmonary fibrosis, confers protection from severe symptoms (p 5.5e-9, OR 0.89). Novel associations to severe symptoms include a lead missense variant in surfactant protein SFTPD previously associated with COPD (p 1.9e-8, OR 1.06), and a missense variant in the lung-expressed transporter SLC22A31 which is co-expressed with surfactant protein genes (p 2.5e-8, OR 1.09). In the current analysis of infected cases, we find a strong protective effect for rs190509934 69 bases from the transcriptional start site of ACE2, a receptor for the spike protein of SARS-CoV-2 (p 3.6e-18, OR 0.69), suggesting genetic variation at ACE2 is associated with protection from SARS-CoV-2 infection. The initiative shows the power of quickly translating genetic data worldwide to biologically relevant findings
