Dataset Information

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

ABSTRACT: A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only one rare pLOF mutation across these genes amongst 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We find no evidence of association of rare loss-of-function variants in the proposed 13 candidate genes with severe COVID-19 outcomes.

SUBMITTER: Povysil G

PROVIDER: S-EPMC7781338 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

Povysil Gundula G Butler-Laporte Guillaume G Shang Ning N Weng Chen C Khan Atlas A Alaamery Manal M Nakanishi Tomoko T Zhou Sirui S Forgetta Vincenzo V Eveleigh Robert R Bourgey Mathieu M Aziz Naveed N Jones Steven S Knoppers Bartha B Scherer Stephen S Strug Lisa L Lepage Pierre P Ragoussis Jiannis J Bourque Guillaume G Alghamdi Jahad J Aljawini Nora N Albes Nour N Al-Afghani Hani M HM Alghamdi Bader B Almutair Mansour M Mahmoud Ebrahim Sabri ES Safie Leen Abu LA Bardisy Hadeel El HE Al Harthi Fawz S FS Alshareef Abdulraheem A Suliman Bandar Ali BA Alqahtani Saleh S AlMalik Abdulaziz A Alrashed May M MM Massadeh Salam S Mooser Vincent V Lathrop Mark M Arabi Yaseen Y Mbarek Hamdi H Saad Chadi C Al-Muftah Wadha W Badji Radja R Al Thani Asma A Ismail Said I SI Gharavi Ali G AG Abedalthagafi Malak S MS Richards J Brent JB Goldstein David B DB Kiryluk Krzysztof K

medRxiv : the preprint server for health sciences 20201221

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. ...[more]

PMID: 33398295

Similar Datasets

Project description:ImportanceAn animal (mouse) study indicated that deficiency of proprotein convertase subtilisin/kexin type 9 (PCSK9) causes cardiac remodeling and heart failure (HF). Cardiac remodeling after PCSK9-inhibitor treatment is a concern for patients and for development of treatment directed against PCSK9.ObjectiveTo determine whether genetic variants in the PCSK9 gene are associated with altered cardiac structure, cardiac function, and HF in humans.Design, setting, participantsThis was a nested case-control study within the UK Biobank. Between March 13, 2006, and October 1, 2010, the UK Biobank enrolled 502 480 individuals aged 40 to 69 years. This study focused on a subset of those individuals, who completed cardiac magnetic resonance (CMR) imaging and had available genetic data. Analyses were conducted between November 2, 2021, and October 28, 2022.ExposuresCarrier status of predicted loss-of-function (pLoF) PCSK9 variants, R46L missense variant, and a genetic risk score (GRS).Main outcomes and measuresA total of 11 CMR imaging measurements, generated using a machine learning algorithm, and HF diagnosis.ResultsIn up to 35 135 individuals with CMR images, 18 252 (52%) were female individuals, and mean (SD) age was 55.0 (7.4) years. No significant association between PCSK9 carrier status and CMR indices were found for left ventricular mass (pLoF: β = -1.01; 95% CI, -2.99 to 0.98; P = .32; R46L: β = -0.18; 95% CI, -0.55 to 0.19; P = .35; GRS: β = -0.19; 95% CI, -0.50 to 0.11; P = .22) and left ventricular ejection fraction (pLoF: β = 0.43; 95% CI, -1.32 to 2.18; P = .63; R46L: β = -0.19; 95% CI, -0.52 to 0.14; P = .26; GRS: β = -0.08; 95% CI, -0.35 to 0.20; P = .58) or HF (pLoF: odds ratio [OR], 1.14; 95% CI, 0.56-2.05; P = .69; R46L: OR, 0.99; 95% CI, 0.90-1.10; P = .91; GRS: OR, 1.04; 95% CI, 0.96-1.13; P = .32).Conclusions and relevanceResults of this case-control study suggest that there was no association between PCSK9 genetic variants and altered cardiac structure, cardiac function, or HF in humans.

Dataset Information

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

Publications

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets