Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
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We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.
Originalsprog | Engelsk |
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Artikelnummer | 5062 |
Tidsskrift | Nature Communications |
Vol/bind | 14 |
Antal sider | 17 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We are grateful to IMI-DIRECT study participants who volunteered for phenotyping, and clinical and technical staff across involved European study centres who contributed to recruitment and clinical assessment of study participants. The work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. Information on the initiatives and activities of the IMI-DIRECT research consortium is available at https://directdiabetes.org .
Publisher Copyright:
© 2023, Springer Nature Limited.
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