Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility

Epidemiological and genetic studies on COVID-19 are currently hindered by inconsistent and limited testing policies to confirm SARS-CoV-2 infection. Recently, it was shown that it is possible to predict COVID-19 cases using cross-sectional self-reported disease-related symptoms. Here, we demonstrate that this COVID-19 prediction model has reasonable and consistent performance across multiple independent cohorts and that our attempt to improve upon this model did not result in improved predictions. Using the existing COVID-19 prediction model, we then conducted a GWAS on the predicted phenotype using a total of 1,865 predicted cases and 29,174 controls. While we did not find any common, large-effect variants that reached genome-wide significance, we do observe suggestive genetic associations at two SNPs (rs11844522, p = 1.9x10-7; rs5798227, p = 2.2x10-7). Explorative analyses furthermore suggest that genetic variants associated with other viral infectious diseases do not overlap with COVID-19 susceptibility and that severity of COVID-19 may have a different genetic architecture compared to COVID-19 susceptibility. This study represents a first effort that uses a symptom-based predicted phenotype as a proxy for COVID-19 in our pursuit of understanding the genetic susceptibility of the disease. We conclude that the inclusion of symptom-based predicted cases could be a useful strategy in a scenario of limited testing, either during the current COVID-19 pandemic or any future viral outbreak..

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

PLoS ONE - 16(2021), 8

Sprache:

Englisch

Beteiligte Personen:

Irene V. van Blokland [VerfasserIn]
Pauline Lanting [VerfasserIn]
Anil P. S. Ori [VerfasserIn]
Judith M. Vonk [VerfasserIn]
Robert C. A. Warmerdam [VerfasserIn]
Johanna C. Herkert [VerfasserIn]
Floranne Boulogne [VerfasserIn]
Annique Claringbould [VerfasserIn]
Esteban A. Lopera-Maya [VerfasserIn]
Meike Bartels [VerfasserIn]
Jouke-Jan Hottenga [VerfasserIn]
Andrea Ganna [VerfasserIn]
Juha Karjalainen [VerfasserIn]
Lifelines COVID-19 cohort study [VerfasserIn]
The COVID-19 Host Genetics Initiative [VerfasserIn]
Caroline Hayward [VerfasserIn]
Chloe Fawns-Ritchie [VerfasserIn]
Archie Campbell [VerfasserIn]
David Porteous [VerfasserIn]
Elizabeth T. Cirulli [VerfasserIn]
Kelly M. Schiabor Barrett [VerfasserIn]
Stephen Riffle [VerfasserIn]
Alexandre Bolze [VerfasserIn]
Simon White [VerfasserIn]
Francisco Tanudjaja [VerfasserIn]
Xueqing Wang [VerfasserIn]
Jimmy M. Ramirez [VerfasserIn]
Yan Wei Lim [VerfasserIn]
James T. Lu [VerfasserIn]
Nicole L. Washington [VerfasserIn]
Eco J. C. de Geus [VerfasserIn]
Patrick Deelen [VerfasserIn]
H. Marike Boezen [VerfasserIn]
Lude H. Franke [VerfasserIn]

Links:

doaj.org [kostenfrei]
www.ncbi.nlm.nih.gov [kostenfrei]
Journal toc [kostenfrei]

Themen:

Medicine
Q
R
Science

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

DOAJ00297164X