A large-scale multi-omics polygenic risk score analysis identified candidate risk locus associated with rheumatoid arthritis - 22/05/25
Highlights |
• | Multi-omics polygenic risk score (PRS) can be used to explore the correlation of biological pathways with specific traits or diseases. |
• | We identified 59 transcriptomics PRS and 29 proteomics PRS significantly associated with RA. |
• | Both proteomics and transcriptomic PRS identified HLA-DQA2 and AGER were significantly associated with RA. |
• | Proteomic PRS from different profiling platforms (SomaScan and Olink) identified a consistent association between TFF3 and RA. |
Abstract |
Objective |
This study aimed to investigate the associations of multi-omics polygenic risk score (PRS) and rheumatoid arthritis (RA) to identify potential genes/proteins and biological pathways.
Methods |
Based on multi-omics data from 48,813 participants in the INTERVAL cohort, we calculated multi-omics PRS for 13,646 mRNAs (RNASeq), 308 proteins (Olink), 2380 proteins (SomaScan), 726 metabolites (Metabolon), and 141 metabolites (Nightingale). Using the generalized linear model, we first evaluated the associations between multi-omics PRS and RA in 58,813 UK Biobank participants. The Gene Ontology (GO) project and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to identify the functional pathways in RA. Furthermore, differential gene expression profile datasets were used to validate the identified genes/proteins in our study.
Results |
We identified 59 transcriptomics PRS and 29 proteomics PRS significantly associated with RA. Both proteomics and transcriptomic PRS identified HLA-DQA2 (RNASeq: OR=1.19, P=1.18×10–24; SomaScan: OR=1.24, P=4.43×10–27) and AGER (RNASeq: OR=0.91, P=4.18×10–4; SomaScan: OR=0.93, P=3.97×10–3) were significantly associated with RA. Proteomic PRS from different profiling platforms (SomaScan and Olink) identified a consistent association between TFF3 (SomaScan: OR=0.90, P=4.08×10–6; Olink: OR=0.93, P=4.87×10–3) and RA. The identified gene/proteins were mainly enriched in the NF-kappa B signaling pathway (hsa04064, P=5.06×10–5) and Cytokine-cytokine receptor interaction (hsa04060, P=2.49×10–4). In addition, a total of 12 candidate genes in our study were verified in two independent GEO datasets, such as FLOT1 and ABCF1.
Conclusion |
Our findings provide novel insights into the involvement of identified genes/proteins and pathways in the pathogenesis of RA from multi-omics levels.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Rheumatoid arthritis (RA), Multi-omics levels, Polygenic risk score (PRS), Biological pathways
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Vol 92 - N° 3
Articolo 105841- maggio 2025 Ritorno al numero
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