A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.
Sirui Zhou,Guillaume Butler-Laporte,Tomoko Nakanishi,David R. Morrison,Jonathan Afilalo,Marc Afilalo,Laetitia Laurent,Maik Pietzner,Nicola D. Kerrison,Kaiqiong Zhao,Elsa Brunet-Ratnasingham,Danielle Henry,Nofar Kimchi,Zaman Afrasiabi,Nardin Rezk,Meriem Bouab,Louis Petitjean,Charlotte Guzman,Xiaoqing Xue,Chris Tselios,Branka Vulesevic,Olumide Adeleye,Tala Abdullah,Noor Almamlouk,Yiheng Chen,Michaël Chassé,Madeleine Durand,Clare Paterson,Johan Normark,Robert Frithiof,Miklos Lipcsey,Michael Hultström,Celia M. T. Greenwood,Hugo Zeberg,Claudia Langenberg,Claudia Langenberg,Elin Thysell,Michael Pollak,Vincent Mooser,Vincenzo Forgetta,Daniel Kaufmann,J. Brent Richards +41 more
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In this article, a two-sample Mendelian randomization (MR) study was conducted to identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding.Abstract:
To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10−8), hospitalization (OR = 0.61, P = 8 × 10−8) and susceptibility (OR = 0.78, P = 8 × 10−6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case–control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development. A variant of the OAS1 gene, which encodes an enzyme that is critical for the innate immune response to viral infections, is associated with decreased risk of death in patients with COVID-19.read more
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Mapping the proteo-genomic convergence of human diseases.
Maik Pietzner,Maik Pietzner,Eleanor Wheeler,Julia Carrasco-Zanini,Adrian Cortes,Mine Koprulu,Maria A. Wörheide,Erin Oerton,James Cook,Isobel D. Stewart,Nicola D. Kerrison,Jian'an Luan,Johannes Raffler,Matthias Arnold,Wiebke Arlt,Stephen O'Rahilly,Gabi Kastenmüller,Eric R. Gamazon,Eric R. Gamazon,Aroon D. Hingorani,Robert A. Scott,Nicholas J. Wareham,Claudia Langenberg,Claudia Langenberg +23 more
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Host genetic factors determining COVID-19 susceptibility and severity.
Thirumalaisamy P. Velavan,Srinivas Reddy Pallerla,Jule Ruter,Yolanda Augustin,Peter G. Kremsner,Sanjeev Krishna,Christian Meyer +6 more
TL;DR: In this article, the authors summarize research on COVID-19 host genetics and compile genetic variants associated with susceptibility to COVID19 and disease severity and discuss candidate genes that should be investigated further to understand such associations and provide insights relevant to pathogenesis, risk classification, therapy response, precision medicine and drug repurposing.
Journal ArticleDOI
Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
Jennifer E. Huffman,Guillaume Butler-Laporte,Atlas Khan,Erola Pairo-Castineira,Theodore G. Drivas,Gina M. Peloso,Tomoko Nakanishi,Andrea Ganna,Anurag Verma,J Kenneth Baillie,Krzysztof Kiryluk,J. Brent Richards,Hugo Zeberg +12 more
TL;DR: In this paper , the OAS1/2/3 cluster was identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13.
Journal ArticleDOI
Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies
Jingning Zhang,Diptavo Dutta,Anna Köttgen,Adrienne Tin,Pascal Schlosser,Morgan E. Grams,Benjamin Harvey,Bing Yu,Eric Boerwinkle,Josef Coresh,Nilanjan Chatterjee +10 more
TL;DR: This paper analyzed data on 4,657 plasma proteins from 7,213 European American (EA) and 1,871 African American (AA) individuals from the Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from African American Study of Kidney Disease and Hypertension study.
Journal ArticleDOI
COVID-19 2022 update: transition of the pandemic to the endemic phase
Michela Biancolella,Vito Luigi Colona,Ruty Mehrian-Shai,Jessica Watt,Lucio Luzzatto,Giuseppe Novelli,Juergen K. V. Reichardt +6 more
TL;DR: In this paper , the authors reviewed the current state of research into the disease with focus on its history, human genetics and genomics and the transition from the pandemic to the endemic phase.
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