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

Butler-Laporte, G.; Povysil, G.; Kosmicki, J.A.; Cirulli, E.T.; Drivas, T.; Furini, S.; Saad, C.; Schmidt, A.; Olszewski, P.; Korotko, U.; Quinodoz, M.; Çelik, E.; Kundu, K.; Walter, K.; Jung, J.; Stockwell, A.D.; Sloofman, L.G.; Jordan, D.M.; Thompson, R.C.; Del Valle, D.; Simons, N.; Cheng, E.; Sebra, R.; Schadt, E.E.; Kim-Schulze, S.; Gnjatic, S.; Merad, M.; Buxbaum, J.D.; Beckmann, N.D.; Charney, A.W.; Przychodzen, B.; Chang, T.; Pottinger, T.D.; Shang, N.; Brand, F.; Fava, F.; Mari, F.; Chwialkowska, K.; Niemira, M.; Pula, S.; Baillie, J.K.; Stuckey, A.; Salas, A.; Bello, X.; Pardo-Seco, J.; Gómez-Carballa, A.; Rivero-Calle, I.; Martinón-Torres, F.; Ganna, A.; Karczewski, K.J.; Veerapen, K.; Bourgey, M.; Bourque, G.; Eveleigh, R.J.; Forgetta, V.; Morrison, D.; Langlais, D.; Lathrop, M.; Mooser, V.; Nakanishi, T.; Frithiof, R.; Hultström, M.; Lipcsey, M.; Marincevic-Zuniga, Y.; Nordlund, J.; Schiabor Barrett, K.M.; Lee, W.; Bolze, A.; White, S.; Riffle, S.; Tanudjaja, F.; Sandoval, E.; Neveux, I.; Dabe, S.; Casadei, N.; Motameny, S.; Alaamery, M.; Massadeh, S.; Aljawini, N.; Almutairi, M.S.; Arabi, Y.M.; Alqahtani, S.A.; Al Harthi, F.S.; Almutairi, A.; Alqubaishi, F.; Alotaibi, S.; Binowayn, A.; Alsolm, E.A.; El Bardisy, H.; Fawzy, M.; Cai, F.; Soranzo, N.; Butterworth, A.; Geschwind, D.H.; Arteaga, S.; Stephens, A.; Butte, M.J.; Boutros, P.C.; Yamaguchi, T.N.; Tao, S.; Eng, S.; Sanders, T.; Tung, P.J.; Broudy, M.E.; Pan, Y.; Gonzalez, A.; Chavan, N.; Johnson, R.; Pasaniuc, B.; Yaspan, B.; Smieszek, S.; Rivolta, C.; Bibert, S.; Bochud, P.Y.; Dabrowski, M.; Zawadzki, P.; Sypniewski, M.; Kaja, E.; Chariyavilaskul, P.; Nilaratanakul, V.; Hirankarn, N.; Shotelersuk, V.; Pongpanich, M.; Phokaew, C.; Chetruengchai, W.; Tokunaga, K.; Sugiyama, M.; Kawai, Y.; Hasegawa, T.; Naito, T.; Namkoong, H.; Edahiro, R.; Kimura, A.; Ogawa, S.; Kanai, T.; Fukunaga, K.; Okada, Y.; Imoto, S.; Miyano, S.; Mangul, S.; Abedalthagafi, M.S.; Zeberg, H.; Grzymski, J.J.; Washington, N.L.; Ossowski, S.; Ludwig, K.U.; Schulte, E.C.; Riess, O.; Moniuszko, M.; Kwasniewski, M.; Mbarek, H.; Ismail, S.I.; Verma, A.; Goldstein, D.B.; Kiryluk, K.; Renieri, A.; Ferreira, MAR; Richards, J.B.

doi:10.1371/journal.pgen.1010367

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

Details

Download: 36327219_BIB_05AB909EB191.pdf (2816.57 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_05AB909EB191

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

PLoS genetics

Author(s)

Butler-Laporte G., Povysil G., Kosmicki J.A., Cirulli E.T., Drivas T., Furini S., Saad C., Schmidt A., Olszewski P., Korotko U., Quinodoz M., Çelik E., Kundu K., Walter K., Jung J., Stockwell A.D., Sloofman L.G., Jordan D.M., Thompson R.C., Del Valle D., Simons N., Cheng E., Sebra R., Schadt E.E., Kim-Schulze S., Gnjatic S., Merad M., Buxbaum J.D., Beckmann N.D., Charney A.W., Przychodzen B., Chang T., Pottinger T.D., Shang N., Brand F., Fava F., Mari F., Chwialkowska K., Niemira M., Pula S., Baillie J.K., Stuckey A., Salas A., Bello X., Pardo-Seco J., Gómez-Carballa A., Rivero-Calle I., Martinón-Torres F., Ganna A., Karczewski K.J., Veerapen K., Bourgey M., Bourque G., Eveleigh R.J., Forgetta V., Morrison D., Langlais D., Lathrop M., Mooser V., Nakanishi T., Frithiof R., Hultström M., Lipcsey M., Marincevic-Zuniga Y., Nordlund J., Schiabor Barrett K.M., Lee W., Bolze A., White S., Riffle S., Tanudjaja F., Sandoval E., Neveux I., Dabe S., Casadei N., Motameny S., Alaamery M., Massadeh S., Aljawini N., Almutairi M.S., Arabi Y.M., Alqahtani S.A., Al Harthi F.S., Almutairi A., Alqubaishi F., Alotaibi S., Binowayn A., Alsolm E.A., El Bardisy H., Fawzy M., Cai F., Soranzo N., Butterworth A., Geschwind D.H., Arteaga S., Stephens A., Butte M.J., Boutros P.C., Yamaguchi T.N., Tao S., Eng S., Sanders T., Tung P.J., Broudy M.E., Pan Y., Gonzalez A., Chavan N., Johnson R., Pasaniuc B., Yaspan B., Smieszek S., Rivolta C., Bibert S., Bochud P.Y., Dabrowski M., Zawadzki P., Sypniewski M., Kaja E., Chariyavilaskul P., Nilaratanakul V., Hirankarn N., Shotelersuk V., Pongpanich M., Phokaew C., Chetruengchai W., Tokunaga K., Sugiyama M., Kawai Y., Hasegawa T., Naito T., Namkoong H., Edahiro R., Kimura A., Ogawa S., Kanai T., Fukunaga K., Okada Y., Imoto S., Miyano S., Mangul S., Abedalthagafi M.S., Zeberg H., Grzymski J.J., Washington N.L., Ossowski S., Ludwig K.U., Schulte E.C., Riess O., Moniuszko M., Kwasniewski M., Mbarek H., Ismail S.I., Verma A., Goldstein D.B., Kiryluk K., Renieri A., Ferreira MAR, Richards J.B.

Working group(s)

COVID-19 Host Genetics Initiative, DeCOI Host Genetics Group, GEN-COVID Multicenter Study (Italy), Mount Sinai Clinical Intelligence Center, GEN-COVID consortium (Spain), GenOMICC Consortium, Japan COVID-19 Task Force, Regeneron Genetics Center

ISSN

1553-7404 (Electronic)

ISSN-L

1553-7390

Publication state

Published

Issued date

11/2022

Peer-reviewed

Oui

Volume

Number

Pages

e1010367

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish

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 = 5.41x10-7). 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.

Keywords

Humans, Exome/genetics, Genome-Wide Association Study, COVID-19/genetics, Genetic Predisposition to Disease, Toll-Like Receptor 7/genetics, SARS-CoV-2/genetics

URN

urn:nbn:ch:serval-BIB_05AB909EB1915

OAI-PMH

oai:serval.unil.ch:BIB_05AB909EB191

DOI

10.1371/journal.pgen.1010367

Pubmed

36327219

Web of science

000925085700002

Open Access

Yes