2 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
- Author
- 23andMe investigators (14122466)
- A Baras (8406552)
- A Justice (13618738)
- A Kousathanas (11759957)
- A Nichol (12113682)
- A Rendon (11760011)
- A Siddiq (11760026)
- A Stuckey (11760038)
- A Tenesa (13967769)
- A Verma (12708896)
- Alexander T. Williams (8751990)
- Altaf Ali (13566445)
- Andrew D. Bretherick (9088544)
- Andy Law (14122475)
- Angie Fawkes (8371179)
- Anna L. Guyatt (8609598)
- B Wang (805040)
- C Hinds (13967766)
- C Kingsley (13967745)
- C Patch (11759996)
- C Summers (7746692)
- CA Odhams (11759993)
- Catherine E Bee (8950487)
- Catherine John (8711869)
- CD Russell (13967715)
- Chiara Batini (3259911)
- Chris P. Ponting (9088550)
- COVID-19 Human Genetics Initiative (14122469)
- D Bentley (7649096)
- D Maslove (13967736)
- D McAuley (13475170)
- D Rhodes (9361013)
- DJ Rader (7635494)
- E Pairo-Castineira (13967709)
- Edward J Hollox (7692299)
- Emma L Adams (8950484)
- F Griffiths (13967721)
- F Maleady-Crowe (11759972)
- G Chan (9853067)
- G Elgar (13967742)
- GenOMICC investigators (14122465)
- GR Abecasis (7696778)
- H Montgomery (10306841)
- J Kenneth Baillie (3875020)
- J Knight (6285983)
- J Millar (9876539)
- JA Kosmicki (13967748)
- James F. Wilson (7638917)
- JE Horowitz (13967751)
- Jian Yang (12136)
- K Morrice (13967727)
- K Rawlik (13967712)
- Kathy Rowan (3742)
- KS Elliott (7655282)
- L Klaric (13367838)
- L Ling (9768971)
- L Todd (10056745)
- Laura D Venn (13566442)
- Lee Murphy (274820)
- Louise V. Wain (110260)
- Loukas Moutsianas (282004)
- M Oetjens (13967760)
- M Shankar-Hari (13398015)
- M Zechner (13967730)
- MAR Ferreira (13967754)
- Mark J. Caulfield (238657)
- Martin D. Tobin (7581161)
- MD Ritchie (7747283)
- MG Semple (7640657)
- N Parkinson (13967733)
- nick Shrine (9026132)
- P Arumugam (11759918)
- P Elliott (7635440)
- P Goddard (9616160)
- P Horby (13727836)
- Paul H. Lee (389909)
- PJM Openshaw (11802437)
- Richard H Scott (13567189)
- Richard J Packer (11075223)
- Robert C. Free (7165082)
- S Donovan (9149219)
- S Keating (13694107)
- S Salehi (9867914)
- S Walker (7719767)
- Sara Clohisey Hendry (14122472)
- T Malinauskas (13967718)
- T Mirshahi (13967757)
- T Walsh (7690706)
- T Zainy (13967739)
- TA Fowler (13967763)
- Veronique Vitart (149854)
- W Oosthuyzen (13967724)
- X Shen (7801967)
- Xueyang Wang (6813818)
- Y Wu (808222)
- Publication venue
- Publication date
- 07/03/2022
- Field of study
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
COVID-19 Host Genetics Initiative. A first update on mapping the human genetic architecture of COVID-19
- Author
- A Cerny (13566592)
- A Conen (13566478)
- A Guillet (13566487)
- A Munting (13566535)
- A Perret (13566628)
- Aarno Palotie (41342)
- Abdolmajid Hosseini (13566952)
- Abdulaziz AlMalik (5215085)
- Abdulraheem Alshareef (3532520)
- Achille Iolascon (206310)
- Adam S Butterworth (3810055)
- Afshar Etemadi Aleagha (13566937)
- Agnese Verzuri (13566721)
- Agostino Ognibene (5624702)
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- Raymond Chung (1955386)
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- Renato Polimanti (3043917)
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- Riccardo Colombo (94203)
- Richard C Trembath (9257558)
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- Rui Li (4631)
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- Ryan C Thompson (13566994)
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- Sabine Claassen (13566256)
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- Salam Massadeh (6628496)
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- Sameer Chavan (3947117)
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- Sandro Mancarella (9467152)
- Sandro Panese (6444245)
- Sang Hyuck Lee (13566892)
- Sanni Ruotsalainen (13566448)
- Sara Alotaibi (13567108)
- Sara Amitrano (9656605)
- Sara Pigazzini (13566247)
- Sarah Alkwai (13567126)
- Sarah Finer (237152)
- Sarah G Earle (13567204)
- Sauro Luchi (13566805)
- Saverio Giuseppe Parisi (4026326)
- Scott T Weiss (9407556)
- Sebastian Garcia-Madrona (13567324)
- Sebastian Zollner (13566925)
- Semira Gonseth Nussle (13566460)
- Serafina Valente (3753733)
- Serena Ludovisi (13566814)
- Serghei Mangul (4973068)
- Sergio Daga (11283239)
- Seyed Behrooz Mohseni Moghaddam (13566943)
- Shaheen Akhtar (192582)
- Shang-Kuan Lin (13567207)
- Shannon McCurdy (11944312)
- Shapna Hussain (13566886)
- Shawn N Murphy (4802670)
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- Shea J Andrews (13566199)
- Shefa Miah (13566901)
- Shefali S Verma (13567090)
- Shona M Kerr (8950520)
- Silvia Baroni (2156290)
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- Simona Dei (13566808)
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- Stefania Mantovani (202342)
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- Stephanie Bibert (316131)
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- Stephen J Wicks (13566349)
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- Vasilios Polymeropoulos (13567237)
- Veronica Rico (13567261)
- Veronica Robles (7338719)
- Veronique Erard (13566466)
- Victor Moreno (748751)
- Vijay G Sankaran (13566175)
- Vincent Mooser (47546)
- Vincenzo Forgetta (756326)
- Voraphoj Nilaratanakul (13566964)
- Vorasuk Shotelersuk (581000)
- Walaa A Felemban (13567150)
- Walaa M El-Lawaty (13566397)
- Walid T Khafaga (13566394)
- Wanna Chetruengchai (9659225)
- Wanying Zhu (1567963)
- Watsamon Jantarabenjakul (9504660)
- WC Albrich (13566586)
- Wei Zhou (24328)
- Wenhan Lu (8908976)
- Werner Albrich (5541584)
- Xavier Farre (10317580)
- Xiao Chang (43560)
- Xiaoqing Xue (6116318)
- Xueyang Wang (6813818)
- Y Lannepoudenx (13566508)
- Yan Sun (22436)
- Yaseen M Arabi (12041017)
- Yasmine Belhaj (13566250)
- Yasser M El-Sherbiny (13566358)
- Yen-Chen Anne Feng (9983636)
- Yuk-Lam Ho (7010873)
- Yuki Bradford (496693)
- Yunsung Lee (10670517)
- Yuval Itan (260527)
- Yves Beguin (264097)
- Zaman Afrasiabi (10905751)
- Zeinab Naderpour (10054118)
- Ziab Z Alahmadey (13567144)
- Publication venue
- Publication date
- 03/08/2022
- Field of study
The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.</p