1. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
- Author
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D’Antonio, Matteo, Nguyen, Jennifer P, Arthur, Timothy D, Matsui, Hiroko, Neale, Benjamin M, Daly, Mark, Ganna, Andrea, Stevens, Christine, Pathak, Gita A, Andrews, Shea J, Kanai, Masahiro, Cordioli, Mattia, Karjalainen, Juha, Polimanti, Renato, Pirinen, Matti, Harerimana, Nadia, Veerapen, Kumar, Wolford, Brooke, Nguyen, Huy, Solomonson, Matthew, Liao, Rachel G, Chwialkowska, Karolina, Trankiem, Amy, Balaconis, Mary K, Hayward, Caroline, Richmond, Anne, Campbell, Archie, Morris, Marcela, Fawns-Ritchie, Chloe, Glessner, Joseph T, Shaw, Douglas M, Chang, Xiao, Polikowski, Hannah, Lauren, E, Chen, Hung-Hsin, Wanying, Zhu, Hakonarson, Hakon, Porteous, David J, Below, Jennifer, North, Kari, McCormick, Joseph B, Timmers, Paul RHJ, Wilson, James F, Tenesa, Albert, D’Mellow, Kenton, Kerr, Shona M, Niemi, Mari EK, Nkambul, Lindokuhle, von Hohenstaufen, Kathrin Aprile, Sobh, Ali, Eltoukhy, Madonna M, Yassen, Amr M, Hegazy, Mohamed AF, Okasha, Kamal, Eid, Mohammed A, Moahmed, Hanteera S, Shahin, Doaa, El-Sherbiny, Yasser M, Elhadidy, Tamer A, Elghafar, Mohamed S Abd, El-Jawhari, Jehan J, Mohamed, Attia AS, Elnagdy, Marwa H, Samir, Amr, Abdel-Aziz, Mahmoud, Khafaga, Walid T, El-Lawaty, Walaa M, Torky, Mohamed S, El-shanshory, Mohamed R, Batini, Chiara, Lee, Paul H, Shrine, Nick, Williams, Alexander T, Tobin, Martin D, Guyatt, Anna L, John, Catherine, Packer, Richard J, Ali, Altaf, Free, Robert C, Wang, Xueyang, Wain, Louise V, Hollox, Edward J, Venn, Laura D, Bee, Catherine E, Adams, Emma L, Niavarani, Ahmadreza, Sharififard, Bahareh, Aliannejad, Rasoul, Amirsavadkouhi, Ali, and Naderpour, Zeinab
- Subjects
Biological Sciences ,Genetics ,Infectious Diseases ,Human Genome ,Coronaviruses Disparities and At-Risk Populations ,Coronaviruses ,Emerging Infectious Diseases ,Lung ,Biotechnology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,COVID-19 ,Chromosome Mapping ,Computational Biology ,Databases ,Genetic ,Ethnicity ,Gene Expression ,Gene Expression Profiling ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Organ Specificity ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,SARS-CoV-2 ,Severity of Illness Index ,Transcriptome ,COVID-19 Host Genetics Initiative ,GWAS ,colocalization ,eQTL ,Biochemistry and Cell Biology ,Medical Physiology ,Biological sciences - 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.
- Published
- 2021