Title: Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
Abstract: 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.
In this talk, I will discuss our experience in forming the largest whole-exome/whole-genome with 21 cohorts across 12 countries. From our finding that 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), which was consistent across sexes, to the more cryptic MARK1 which was associated with a 23.9-fold increase in the odds of severe disease (95% CI: 6.5–88.2, p = 1.89x10-6). Most importantly, since this was the first collaboration of this scale looking at rare variants, I will discuss the lessons we learned, how we could have improved on them, and what I would do differently in a future program like this.
Biography: Guillaume Butler-Laporte is a clinician-scientist from at the McGill University Health Centre in Montreal, Canada. He is a consultant in infectious diseases and genetic epidemiologist who was actively involved in the scientific response to the COVID-19 pandemic and the COVID-19 Host Genetic Initiative when he was working in professor Brent Richards’s lab and the Biobanque Québécoise de la COVID-19. He led the COVID-19 HGI’s working group on rare variants and whole-genome/whole-exome sequencing. He is currently a Canadian Institutes of Health Research fellow at the University of Oxford in the Mentzer-Hill lab until his return to McGill in 2024.
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