Multimodal Integration of Protein Interactomes With Genomic and Molecular Data Discovers Distinct Rheumatoid Arthritis Endotypes
Authors' conclusion
Our findings demonstrate the use of network-based approaches in revealing differential genetic risk factors underlying CCP+/RF+ and CCP-/RF+ RA. Disease-associated gene modules detected in synovial tissue were also observed in peripheral blood, indicating joint-specific molecular programs are reflected systemically.
Study context
- Population
- Patients with Rheumatoid Arthritis (RA) in the Rheumatoid Arthritis Comparative Effectiveness Research cohort
- Participants
- 555 vs 384
- Comparison
- CCP+/RF+ RA vs CCP-/RF+ RA
- CCP+/RF+ RAn = 555
- CCP-/RF+ RAn = 384reference
- Outcome
- Genetic differences between CCP+/RF+ and CCP-/RF+ RA
Methodological detailsnetwork-based genome-wide association study (GWAS), multiomic integration
- Network-based GWAS
- Multiomic integration
Main finding
As reported in the abstract
Putative gene modules (incl. many genes outside HLA loci) explaining genetic differences
14
Modules validated by heritability partitioning and multivariate expression analyses
4
Further findings
Module functional significance
- Established using multiple orthogonal cohorts
Original publication
Multimodal Integration of Protein Interactomes With Genomic and Molecular Data Discovers Distinct Rheumatoid Arthritis Endotypes. Arthritis Rheumatol. Published 9 March 2026. doi:10.
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