September 25, 2024
Keio University
Osaka University
The University of Tokyo
RIKEN
Japan Science and Technology Agency (JST)
The joint research group "COVID-19 Task Force," established to combat the threat of the novel coronavirus disease (COVID-19) caused by SARS-CoV-2, has previously presented important findings, such as the elucidation of factors contributing to severe COVID-19. Now, a research group led by Associate Professor Qingbo Wang (at the time of the research, Department of Genetics, Graduate School of Medicine, The University of Tokyo), Professor Yukinori Okada (Department of Genetic Statistics, Graduate School of Medicine, Osaka University / Department of Genetics, Graduate School of Medicine, The University of Tokyo / Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences), and Senior Lecturer Min-Goo Seo (Department of Infectious Diseases, School of Medicine, Keio University), has identified on a large scale human genomic sequences that contribute to individual differences in plasma protein levels through a comprehensive analysis of plasma proteins using samples from 1,405 COVID-19 patients.
In this study, by comparing 582 human genomic variants that control plasma protein expression and have been precisely estimated (fine-mapped) as causal variants in previous studies, and by integrally analyzing protein functional information, it was shown that the probability of causal variants being missense or loss-of-function variants is more than 1,000 times higher. Furthermore, through comparisons with blood mRNA expression levels, evaluation of associations with complex traits such as diseases, and analysis of interactions with COVID-19 severity, the study clarified the diverse factors that determine protein expression in plasma and also demonstrated the widespread existence of associations with diseases that cannot be identified by mRNA expression alone. These results are expected to lead to a more detailed understanding of the association of complex traits through the regulation of gene expression by individual genomic differences.
The results of this research were published in the online edition of the international scientific journal Nature Genetics on September 24, 2024 (UK time). The COVID-19 Task Force will continue its activities as a public good for society to prepare for future pandemics.
For the full press release, please see below.