Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative

Butler-Laporte, Guillaume and Povysil, Gundula and Kosmicki, Jack A. and Cirulli, Elizabeth T. and Drivas, Theodore and Furini, Simone and Saad, Chadi and Schmidt, Axel and Olszewski, Pawel and Korotko, Urszula and Quinodoz, Mathieu and Çelik, Elifnaz and Kundu, Kousik and Walter, Klaudia and Jung, Junghyun and Stockwell, Amy D. and Sloofman, Laura G. and Jordan, Daniel M. and Thompson, Ryan C. and Del Valle, Diane and Simons, Nicole and Cheng, Esther and Sebra, Robert and Schadt, Eric E. and Kim-Schulze, Seunghee and Gnjatic, Sacha and Merad, Miriam and Buxbaum, Joseph D. and Beckmann, Noam D. and Charney, Alexander W. and Przychodzen, Bartlomiej and Chang, Timothy and Pottinger, Tess D. and Shang, Ning and Brand, Fabian and Fava, Francesca and Mari, Francesca and Chwialkowska, Karolina and Niemira, Magdalena and Pula, Szymon and Baillie, J. Kenneth and Stuckey, Alex and Salas, Antonio and Bello, Xabier and Pardo-Seco, Jacobo and Gómez-Carballa, Alberto and Rivero-Calle, Irene and Martinón-Torres, Federico and Ganna, Andrea and Karczewski, Konrad J. and Veerapen, Kumar and Bourgey, Mathieu and Bourque, Guillaume and Eveleigh, Robert Jm and Forgetta, Vincenzo and Morrison, David and Langlais, David and Lathrop, Mark and Mooser, Vincent and Nakanishi, Tomoko and Frithiof, Robert and Hultström, Michael and Lipcsey, Miklos and Marincevic-Zuniga, Yanara and Nordlund, Jessica and Schiabor Barrett, Kelly M. and Lee, William and Bolze, Alexandre and White, Simon and Riffle, Stephen and Tanudjaja, Francisco and Sandoval, Efren and Neveux, Iva and Dabe, Shaun and Casadei, Nicolas and Motameny, Susanne and Alaamery, Manal and Massadeh, Salam and Aljawini, Nora and Almutairi, Mansour S. and Arabi, Yaseen M. and Alqahtani, Saleh A. and Al Harthi, Fawz S. and Almutairi, Amal and Alqubaishi, Fatima and Alotaibi, Sarah and Binowayn, Albandari and Alsolm, Ebtehal A. and El Bardisy, Hadeel and Fawzy, Mohammad and Cai, Fang and Soranzo, Nicole and Butterworth, Adam and DeCOI Host Genetics Group, and GEN-Covid Multicenter Study, and Mount Sinai Clinical Intelligence Center, and GEN-Covid consortium, and GenOmicc Consortium, and Regeneron Genetics Center, and Geschwind, Daniel H. and Arteaga, Stephanie and Stephens, Alexis and Butte, Manish J. and Boutros, Paul C. and Yamaguchi, Takafumi N. and Tao, Shu and Eng, Stefan and Sanders, Timothy and Tung, Paul J. and Broudy, Michael E. and Pan, Yu and Gonzalez, Alfredo and Chavan, Nikhil and Johnson, Ruth and Pasaniuc, Bogdan and Yaspan, Brian and Smieszek, Sandra and Rivolta, Carlo and Bibert, Stephanie and Bochud, Pierre-Yves and Dabrowski, Maciej and Zawadzki, Pawel and Sypniewski, Mateusz and Kaja, Elżbieta and Chariyavilaskul, Pajaree and Nilaratanakul, Voraphoj and Hirankarn, Nattiya and Shotelersuk, Vorasuk and Pongpanich, Monnat and Phokaew, Chureerat and Chetruengchai, Wanna and Tokunaga, Katsushi and Sugiyama, Masaya and Kawai, Yosuke and Hasegawa, Takanori and Naito, Tatsuhiko and Namkoong, Ho and Edahiro, Ryuya and Kimura, Akinori and Ogawa, Seishi and Kanai, Takanori and Fukunaga, Koichi and Okada, Yukinori and Imoto, Seiya and Miyano, Satoru and Mangul, Serghei and Abedalthagafi, Malak S. and Zeberg, Hugo and Grzymski, Joseph J. and Washington, Nicole L. and Ossowski, Stephan and Ludwig, Kerstin U. and Schulte, Eva C. and Riess, Olaf and Moniuszko, Marcin and Kwasniewski, Miroslaw and Mbarek, Hamdi and Ismail, Said I. and Verma, Anurag and Goldstein, David B. and Kiryluk, Krzysztof and Renieri, Alessandra and Ferreira, Manuel A. R. and Richards, J. Brent. (2022) Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative. PLoS Genetics, 18 (11). e1010367.

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Official URL: https://edoc.unibas.ch/95550/

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Ophthalmologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Ophthalmologie USB
09 Associated Institutions > Institute of Molecular and Clinical Ophthalmology Basel (IOB) > Research Group Rivolta IOB
UniBasel Contributors:Rivolta, Carlo
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Sep 2023 07:27
Deposited On:20 Sep 2023 07:27

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