A large-scale multi-omics polygenic risk score analysis identified candidate risk locus associated with rheumatoid arthritis
Authors' conclusion
Our findings provide novel insights into the involvement of identified genes/proteins and pathways in the pathogenesis of RA from multi-omics levels.
Study context
- Population
- UK Biobank participants; multi-omics polygenic risk score (PRS) derived from INTERVAL cohort data (48,813 participants)UK Biobank
- Participants
- 58,813 participants
- Outcome
- Associations between multi-omics PRS and RA
Methodological detailsmulti-omics polygenic risk score analysis, generalized linear model, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, validation in two independent GEO datasets
- Multi-omics polygenic risk score analysis
- Generalized linear model
- GO and KEGG pathway analysis
- Validation in two independent GEO datasets
Performance
As reported in the abstract
Multi-omics PRS associated with RA
- Transcriptomics PRS significantly associated with rheumatoid arthritis (RA)
- 59
- Proteomics PRS significantly associated with RA
- 29
- HLA-DQA2, RNASeq PRS: OR
- 1.19 (P=1.18×10-24)
- HLA-DQA2, SomaScan PRS: OR
- 1.24 (P=4.43×10-27)
- AGER, RNASeq PRS: OR
- 0.91 (P=4.18×10-4)
- AGER, SomaScan PRS: OR
- 0.93 (P=3.97×10-3)
- TFF3, SomaScan PRS: OR
- 0.90 (P=4.08×10-6)
- TFF3, Olink PRS: OR
- 0.93 (P=4.87×10-3)
Further findings
Pathway enrichment of identified genes/proteins
- NF-kappa B signaling pathway (hsa04064)
- P = 5.06×10-5
- Cytokine-cytokine receptor interaction (hsa04060)
- P = 2.49×10-4
Candidate genes verified in two independent GEO datasets
- Candidate genes verified (e.g., FLOT1 and ABCF1)
- 12
Original publication
A large-scale multi-omics polygenic risk score analysis identified candidate risk locus associated with rheumatoid arthritis. Joint Bone Spine. Published 26 December 2024. doi:10.
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