1. Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
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Guillaume, Butler-Laporte, Gundula, Povysil, Kosmicki, Jack A., Cirulli, Elizabeth T., Theodore, Drivas, Furini, Simone, Chadi, Saad, Axel, Schmidt, Pawel, Olszewski, Urszula, Korotko, Mathieu, Quinodoz, Elifnaz, Çelik, Kousik, Kundu, Klaudia, Walter, Junghyun, Jung, Stockwell, Amy D., Sloofman, Laura G., Jordan, Daniel M., Thompson, Ryan C., Diane Del Valle, Nicole, Simons, Esther, Cheng, Robert, Sebra, Schadt, Eric E., Seunghee, Kim-Schulze, Sacha, Gnjatic, Miriam, Merad, Buxbaum, Joseph D., Beckmann, Noam D., Charney, Alexander W., Bartlomiej, Przychodzen, Timothy, Chang, Pottinger, Tess D., Ning, Shang, Fabian, Brand, Fava, Francesca, Mari, Francesca, Karolina, Chwialkowska, Magdalena, Niemira, Szymon, Pula, J Kenneth Baillie, Alex, Stuckey, Antonio, Salas, Xabier, Bello, Jacobo, Pardo-Seco, Alberto, Gómez-Carballa, Irene, Rivero-Calle, Federico, Martinón-Torres, Andrea, Ganna, Karczewski, Konrad J., Kumar, Veerapen, Mathieu, Bourgey, Guillaume, Bourque, Robert JM Eveleigh, Vincenzo, Forgetta, David, Morrison, David, Langlais, Mark, Lathrop, Vincent, Mooser, Tomoko, Nakanishi, Robert, Frithiof, Michael, Hultström, Miklos, Lipcsey, Yanara, Marincevic-Zuniga, Jessica, Nordlund, Schiabor Barrett, Kelly M., William, Lee, Alexandre, Bolze, Simon, White, Stephen, Riffle, Francisco, Tanudjaja, Efren, Sandoval, Iva, Neveux, Shaun, Dabe, Nicolas, Casadei, Susanne, Motameny, Manal, Alaamery, Salam, Massadeh, Nora, Aljawini, Almutairi, Mansour S., Arabi, Yaseen M., Alqahtani, Saleh A., Al Harthi, Fawz S., Amal, Almutairi, Fatima, Alqubaishi, Sarah, Alotaibi, Albandari, Binowayn, Alsolm, Ebtehal A., Hadeel El Bardisy, Mohammad, Fawzy, Fang, Cai, Nicole, Soranzo, Adam, Butterworth, COVID-19 Host Genetics Initiative, DeCOI Host Genetics Group, GEN-COVID Multicenter Study (Italy), Daga, Sergio, Meloni, Ilaria, Mount Sinai Clinical Intelligence Center, GEN-COVID consortium (Spain), Genomicc, Consortium, Japan COVID-19 Task Force, Regeneron Genetics Center, Geschwind, Daniel H., Stephanie, Arteaga, Alexis, Stephens, Butte, Manish J., Boutros, Paul C., Yamaguchi, Takafumi N., Shu, Tao, Stefan, Eng, Timothy, Sanders, Tung, Paul J., Broudy, Michael E., Pan, Yu, Alfredo, Gonzalez, Nikhil, Chavan, Ruth, Johnson, Bogdan, Pasaniuc, Brian, Yaspan, Sandra, Smieszek, Carlo, Rivolta, Stephanie, Bibert, Pierre-Yves, Bochud, Maciej, Dabrowski, Pawel, Zawadzki, Mateusz, Sypniewski, Elżbieta, Kaja, Pajaree, Chariyavilaskul, Voraphoj, Nilaratanakul, Nattiya, Hirankarn, Vorasuk, Shotelersuk, Monnat, Pongpanich, Chureerat, Phokaew, Wanna, Chetruengchai, Katsushi, Tokunaga, Masaya, Sugiyama, Yosuke, Kawai, Takanori, Hasegawa, Tatsuhiko, Naito, Namkoong, Ho, Ryuya, Edahiro, Akinori, Kimura, Seishi, Ogawa, Takanori, Kanai, Koichi, Fukunaga, Yukinori, Okada, Seiya, Imoto, Satoru, Miyano, Serghei, Mangul, Abedalthagafi, Malak S., Hugo, Zeberg, Grzymski, Joseph J., Washington, Nicole L., Stephan, Ossowski, Ludwig, Kerstin U., Schulte, Eva C., Olaf, Riess, Marcin, Moniuszko, Miroslaw, Kwasniewski, Hamdi, Mbarek, Ismail, Said I., Anurag, Verma, Goldstein, David B., Krzysztof, Kiryluk, Renieri, Alessandra, Ferreira, Manuel A. R., J Brent Richards, Butler-Laporte, Guillaume, Povysil, Gundula, Kosmicki, Jack A, Cirulli, Elizabeth T, Drivas, Theodore, Furini, Simone, Saad, Chadi, Schmidt, Axel, Olszewski, Pawel, Korotko, Urszula, Quinodoz, Mathieu, Çelik, Elifnaz, Kundu, Kousik, Walter, Klaudia, Jung, Junghyun, Stockwell, Amy D, Sloofman, Laura G, Jordan, Daniel M, Thompson, Ryan C, Del Valle, Diane, Simons, Nicole, Cheng, Esther, Sebra, Robert, Schadt, Eric E, Kim-Schulze, Seunghee, Gnjatic, Sacha, Merad, Miriam, Buxbaum, Joseph D, Beckmann, Noam D, Charney, Alexander W, Przychodzen, Bartlomiej, Chang, Timothy, Pottinger, Tess D, Shang, Ning, Brand, Fabian, Fava, Francesca, Mari, Francesca, Chwialkowska, Karolina, Niemira, Magdalena, Pula, Szymon, Baillie, J Kenneth, Stuckey, Alex, Salas, Antonio, Bello, Xabier, Pardo-Seco, Jacobo, Gómez-Carballa, Alberto, Rivero-Calle, Irene, Martinón-Torres, Federico, Ganna, Andrea, Karczewski, Konrad J, Veerapen, Kumar, Bourgey, Mathieu, Bourque, Guillaume, Eveleigh, Robert Jm, Forgetta, Vincenzo, Morrison, David, Langlais, David, Lathrop, Mark, Mooser, Vincent, Nakanishi, Tomoko, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Marincevic-Zuniga, Yanara, Nordlund, Jessica, Schiabor Barrett, Kelly M, Lee, William, Bolze, Alexandre, White, Simon, Riffle, Stephen, Tanudjaja, Francisco, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Casadei, Nicola, Motameny, Susanne, Alaamery, Manal, Massadeh, Salam, Aljawini, Nora, Almutairi, Mansour S, Arabi, Yaseen M, Alqahtani, Saleh A, Al Harthi, Fawz S, Almutairi, Amal, Alqubaishi, Fatima, Alotaibi, Sarah, Binowayn, Albandari, Alsolm, Ebtehal A, El Bardisy, Hadeel, Fawzy, Mohammad, Cai, Fang, Soranzo, Nicole, Butterworth, Adam, Geschwind, Daniel H, Arteaga, Stephanie, Stephens, Alexi, Butte, Manish J, Boutros, Paul C, Yamaguchi, Takafumi N, Tao, Shu, Eng, Stefan, Sanders, Timothy, Tung, Paul J, Broudy, Michael E, Pan, Yu, Gonzalez, Alfredo, Chavan, Nikhil, Johnson, Ruth, Pasaniuc, Bogdan, Yaspan, Brian, Smieszek, Sandra, Rivolta, Carlo, Bibert, Stephanie, Bochud, Pierre-Yve, Dabrowski, Maciej, Zawadzki, Pawel, Sypniewski, Mateusz, Kaja, Elżbieta, Chariyavilaskul, Pajaree, Nilaratanakul, Voraphoj, Hirankarn, Nattiya, Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Tokunaga, Katsushi, Sugiyama, Masaya, Kawai, Yosuke, Hasegawa, Takanori, Naito, Tatsuhiko, Namkoong, Ho, Edahiro, Ryuya, Kimura, Akinori, Ogawa, Seishi, Kanai, Takanori, Fukunaga, Koichi, Okada, Yukinori, Imoto, Seiya, Miyano, Satoru, Mangul, Serghei, Abedalthagafi, Malak S, Zeberg, Hugo, Grzymski, Joseph J, Washington, Nicole L, Ossowski, Stephan, Ludwig, Kerstin U, Schulte, Eva C, Riess, Olaf, Moniuszko, Marcin, Kwasniewski, Miroslaw, Mbarek, Hamdi, Ismail, Said I, Verma, Anurag, Goldstein, David B, Kiryluk, Krzysztof, Renieri, Alessandra, Ferreira, Manuel A R, Richards, J Brent, Data Science Genetic Epidemiology Lab, Institute for Molecular Medicine Finland, University of Helsinki, and Helsinki Institute of Life Science HiLIFE
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Infectious Medicine ,Cancer Research ,Host genetics is a key determinant of COVID-19 outcomes. Previously ,Infektionsmedicin ,variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence ,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 ,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 ,studying rare variants may provide additional insights into disease susceptibility and pathogenesis ,Genetics ,Humans ,Exome ,Genetic Predisposition to Disease ,Molecular Biology ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Medicinsk genetik ,SARS-CoV-2 ,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 ,1184 Genetics, developmental biology, physiology ,COVID-19 ,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 ,737 controls ,Toll-Like Receptor 7 ,the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However ,085 severe disease cases and 571 ,thereby informing therapeutics development. Here ,Medical Genetics ,Genome-Wide Association Study - Abstract
Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.
- Published
- 2022