학술논문
Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
Document Type
Report
Author
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, Miklos; 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, Nicolas; 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, Alexis; 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-Yves; Dabrowski, Maciej; Zawadzki, Pawel; Sypniewski, Mateusz; Kaja, Elzbieta; 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
Source
PLoS Genetics. November 3, 2022, Vol. 18 Issue 11, pe1010367
Subject
Language
English
ISSN
1553-7390
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. 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.sup.-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.
Author(s): Guillaume Butler-Laporte 1,2, Gundula Povysil 3, Jack A. Kosmicki 4, Elizabeth T. Cirulli 5, Theodore Drivas 6,7,8, Simone Furini 9, Chadi Saad 10, Axel Schmidt 11, Pawel Olszewski 12, [...]
Author(s): Guillaume Butler-Laporte 1,2, Gundula Povysil 3, Jack A. Kosmicki 4, Elizabeth T. Cirulli 5, Theodore Drivas 6,7,8, Simone Furini 9, Chadi Saad 10, Axel Schmidt 11, Pawel Olszewski 12, [...]