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

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Butler-Laporte, G (author)

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

Article/chapterEnglish2022

Publisher, publication year, extent ...

2022-11-03
Public Library of Science (PLoS),2022

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LIBRIS-ID:oai:prod.swepub.kib.ki.se:151972618
http://kipublications.ki.se/Default.aspx?queryparsed=id:151972618URI
https://doi.org/10.1371/journal.pgen.1010367DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-488649URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

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Povysil, G (author)
Kosmicki, JA (author)
Cirulli, ET (author)
Drivas, T (author)
Furini, S (author)
Saad, C (author)
Schmidt, A (author)
Olszewski, P (author)
Korotko, U (author)
Quinodoz, M (author)
Celik, E (author)
Kundu, K (author)
Walter, K (author)
Jung, J (author)
Stockwell, AD (author)
Sloofman, LG (author)
Jordan, DM (author)
Thompson, RC (author)
Del Valle, D (author)
Simons, N (author)
Cheng, E (author)
Sebra, R (author)
Schadt, EE (author)
Kim-Schulze, S (author)
Gnjatic, S (author)
Merad, M (author)
Buxbaum, JD (author)
Beckmann, ND (author)
Charney, AW (author)
Przychodzen, B (author)
Chang, T (author)
Pottinger, TD (author)
Shang, N (author)
Brand, F (author)
Fava, F (author)
Mari, F (author)
Chwialkowska, K (author)
Niemira, M (author)
Pula, S (author)
Baillie, JK (author)
Stuckey, A (author)
Salas, A (author)
Bello, X (author)
Pardo-Seco, J (author)
Gomez-Carballa, A (author)
Rivero-Calle, I (author)
Martinon-Torres, F (author)
Ganna, A (author)
Karczewski, KJ (author)
Veerapen, K (author)
Bourgey, M (author)
Bourque, G (author)
Eveleigh, RJ (author)
Forgetta, V (author)
Morrison, D (author)
Langlais, D (author)
Lathrop, M (author)
Mooser, V (author)
Nakanishi, T (author)
Frithiof, RobertUppsala universitet,Anestesiologi och intensivvård(Swepub:uu)robfr118 (author)
Hultström, Michael,1978-Uppsala universitet,Anestesiologi och intensivvård,Integrativ Fysiologi,Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada;Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada.(Swepub:uu)mihul498 (author)
Lipcsey, MiklósUppsala universitet,Hedenstiernalaboratoriet(Swepub:uu)milip123 (author)
Marincevic-Zuniga, YanaraUppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab,Molecular Precision Medicine(Swepub:uu)yanma214 (author)
Nordlund, JessicaUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär precisionsmedicin(Swepub:uu)jesno775 (author)
Barrett, KMS (author)
Lee, W (author)
Bolze, A (author)
White, S (author)
Riffle, S (author)
Tanudjaja, F (author)
Sandoval, E (author)
Neveux, I (author)
Dabe, S (author)
Casadei, N (author)
Motameny, S (author)
Alaamery, M (author)
Massadeh, S (author)
Aljawini, N (author)
Almutairi, MS (author)
Arabi, YM (author)
Alqahtani, SA (author)
Al Harthi, FS (author)
Almutairi, A (author)
Alqubaishi, F (author)
Alotaibi, S (author)
Binowayn, A (author)
Alsolm, EA (author)
El Bardisy, H (author)
Fawzy, M (author)
Cai, F (author)
Soranzo, N (author)
Butterworth, A (author)
Geschwind, DH (author)
Arteaga, S (author)
Stephens, A (author)
Butte, MJ (author)
Boutros, PC (author)
Yamaguchi, TN (author)
Tao, S (author)
Eng, S (author)
Sanders, T (author)
Tung, PJ (author)
Broudy, ME (author)
Pan, Y (author)
Gonzalez, A (author)
Chavan, N (author)
Johnson, R (author)
Pasaniuc, B (author)
Yaspan, B (author)
Smieszek, S (author)
Rivolta, C (author)
Bibert, S (author)
Bochud, PY (author)
Dabrowski, M (author)
Zawadzki, P (author)
Sypniewski, M (author)
Kaja, E (author)
Chariyavilaskul, P (author)
Nilaratanakul, V (author)
Hirankarn, N (author)
Shotelersuk, V (author)
Pongpanich, M (author)
Phokaew, C (author)
Chetruengchai, W (author)
Tokunaga, K (author)
Sugiyama, M (author)
Kawai, Y (author)
Hasegawa, T (author)
Naito, T (author)
Namkoong, H (author)
Edahiro, R (author)
Kimura, A (author)
Ogawa, S (author)
Kanai, T (author)
Fukunaga, K (author)
Okada, Y (author)
Imoto, S (author)
Miyano, S (author)
Mangul, S (author)
Abedalthagafi, MS (author)
Zeberg, HKarolinska Institutet (author)
Grzymski, JJ (author)
Washington, NL (author)
Ossowski, S (author)
Ludwig, KU (author)
Schulte, EC (author)
Riess, O (author)
Moniuszko, M (author)
Kwasniewski, M (author)
Mbarek, H (author)
Ismail, SI (author)
Verma, A (author)
Goldstein, DB (author)
Kiryluk, K (author)
Renieri, A (author)
Ferreira, MAR (author)
Richards, JB (author)
Uppsala universitetAnestesiologi och intensivvård (creator_code:org_t)

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In:PLoS genetics: Public Library of Science (PLoS)18:11, s. e1010367-1553-74041553-7390

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By the author/editor: Butler-Laporte, ...; Povysil, G; Kosmicki, JA; Cirulli, ET; Drivas, T; Furini, S; show more...; Saad, C; Schmidt, A; Olszewski, P; Korotko, U; Quinodoz, M; Celik, E; Kundu, K; Walter, K; Jung, J; Stockwell, AD; Sloofman, LG; Jordan, DM; Thompson, RC; Del Valle, D; Simons, N; Cheng, E; Sebra, R; Schadt, EE; Kim-Schulze, S; Gnjatic, S; Merad, M; Buxbaum, JD; Beckmann, ND; Charney, AW; Przychodzen, B; Chang, T; Pottinger, TD; Shang, N; Brand, F; Fava, F; Mari, F; Chwialkowska, K; Niemira, M; Pula, S; Baillie, JK; Stuckey, A; Salas, A; Bello, X; Pardo-Seco, J; Gomez-Carballa, ...; Rivero-Calle, I; Martinon-Torres, ...; Ganna, A; Karczewski, KJ; Veerapen, K; Bourgey, M; Bourque, G; Eveleigh, RJ; Forgetta, V; Morrison, D; Langlais, D; Lathrop, M; Mooser, V; Nakanishi, T; Frithiof, Robert; Hultström, Micha ...; Lipcsey, Miklós; Marincevic-Zunig ...; Nordlund, Jessic ...; Barrett, KMS; 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, MS; Arabi, YM; Alqahtani, SA; Al Harthi, FS; Almutairi, A; Alqubaishi, F; Alotaibi, S; Binowayn, A; Alsolm, EA; El Bardisy, H; Fawzy, M; Cai, F; Soranzo, N; Butterworth, A; Geschwind, DH; Arteaga, S; Stephens, A; Butte, MJ; Boutros, PC; Yamaguchi, TN; Tao, S; Eng, S; Sanders, T; Tung, PJ; Broudy, ME; Pan, Y; Gonzalez, A; Chavan, N; Johnson, R; Pasaniuc, B; Yaspan, B; Smieszek, S; Rivolta, C; Bibert, S; Bochud, PY; Dabrowski, M; Zawadzki, P; Sypniewski, M; Kaja, E; Chariyavilaskul, ...; 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 ...; Zeberg, H; Grzymski, JJ; Washington, NL; Ossowski, S; Ludwig, KU; Schulte, EC; Riess, O; Moniuszko, M; Kwasniewski, M; Mbarek, H; Ismail, SI; Verma, A; Goldstein, DB; Kiryluk, K; Renieri, A; Ferreira, MAR; Richards, JB; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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