TY - JOUR
AU - Baillie, J. Kenneth
PY - 2022
DA - November
TI - Exome-wide association study to identify rare variants influencing COVID-19 outcomes:Results from the Host Genetics Initiative
JO - PLoS Genetics
EP - 26
VL - 18
IS - 11
DO - https://doi.org/10.1371/journal.pgen.1010367
AB - Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
PB - Public Library of Science
UR - https://www.research.ed.ac.uk/en/publications/fd2f1664-54b4-48e6-9520-23766c98e522
KW - Coronavirus (COVID-19)
ER