SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
Matteo D’Antonio, Jennifer Nguyen, Timothy D. Arthur, Hiroko Matsui, Agnieszka D’Antonio‐Chronowska, Kelly A. Frazer, Benjamin M. Neale, Mark J. Daly, Andrea Ganna, Christine Stevens, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Mattia Cordioli, Andrea Ganna, Juha Karjalainen, Gita A. Pathak, Renato Polimanti, Shea J. Andrews, Mattia Cordioli, Matti Pirinen, Masahiro Kanai, Nadia V. Harerimana, Kumar Veerapen, Brooke Wolford, Huy Nguyen, Matthew Solomonson, Christine Stevens, Rachel G. Liao, Karolina Chwiałkowska, Amy Trankiem, Mary K. Balaconis, Caroline Hayward, Anne Richmond, Archie Campbell, Marcela Morris, Chloe Fawns‐Ritchie, Joseph Glessner, Douglas M. Shaw, Xiao Chang, Hannah Polikowski, Petty E. Lauren, Hung‐Hsin Chen, Wanying Zhu, Håkon Håkonarson, David J. Porteous, Jennifer E. Below, K.E. North, Joseph B. McCormick, Paul R. H. J. Timmers, James F. Wilson, Albert Tenesa, Kenton D’Mellow, Shona M. Kerr, Mari E.K. Niemi, Mattia Cordioli, Lindokuhle Nkambul, Kathrin Aprile von Hohenstaufen, Ali Sobh, Madonna M. Eltoukhy, Amr M. Yassen, M. Hegazy, Kamal Okasha, Mohammed Eid, Hanteera S. Moahmed, Doaa Shahin, Yasser M. El‐Sherbiny, Tamer Elhadidy, Mohamed S. Abd Elghafar, Jehan J. El‐Jawhari, Attia A. S. Mohamed, Marwa H. Elnagdy, Amr Samir, Mahmoud Abdel-Aziz, Walid T. Khafaga, Walaa M. El-Lawaty, Mohamed Torky, Mohamed El‐Shanshory, Chiara Batini, Paul H. Lee, Nick Shrine, Alexander T. Williams, Martin D. Tobin, Anna L. Guyatt, Catherine John, Richard Packer, Altaf Ali, Robert C. Free, Xueyang Wang, Louise V. Wain, Edward J. Hollox, Laura D. Venn, Catherine Bee, Emma L. Adams, Mari E.K. Niemi, Ahmadreza Niavarani, Mattia Cordioli, Lindokuhle Nkambul, Bahareh Sharififard, Rasoul Aliannejad
Abstract
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types.