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

Butler-Laporte, G (author)
Povysil, G (author)
Kosmicki, JA (author)
show more...
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, Robert (author)
Uppsala universitet,Anestesiologi och intensivvård
Hultström, Michael, 1978- (author)
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.
Lipcsey, Miklós (author)
Uppsala universitet,Hedenstiernalaboratoriet
Marincevic-Zuniga, Yanara (author)
Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab,Molecular Precision Medicine
Nordlund, Jessica (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär precisionsmedicin
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, H (author)
Karolinska Institutet
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)
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 (creator_code:org_t)
2022-11-03
2022
English.
In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

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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
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Infectious Medic ...
Articles in the publication
PLoS genetics
By the university
Karolinska Institutet
Uppsala University

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