Work

Combining A Massively Parallel Reporter Assay and Human Data to Elucidate Genetic Mechanisms Driving Risk for Juvenile Idiopathic Arthritis

Year: 2026

Type: preprint

Abstract: Background: While progress has been made in identifying the true risk-driving single nucleotide polymorphisms (SNPS) on juvenile idiopathic arthritis (JIA) risk haplotypes, the affected cells and target genes largely remain unknown. Methods: We used data from a previously published massively parallel reporter assay (MPRA) to query human data in the Database of Immune Cell eQTLs (DICE) and the Gene-Tissue Expression (GTEx) database to identify affected cells and target genes of MPRA-identified SNPs in immune cells and relevant tissues. Results: SNPs identified on MPRA were associated with gene expression levels in a broad range of immune cells in the DICE database, including CD4+ and CD8+ T lymphocytes, monocytes, NK cells, and B cells. MPRA-identified SNPs showed strong associations with gene expression in GTEx whole blood, spleen, and/or EBV-transformed lymphocytes. Conclusions: Our data show the efficacy of combining MPRA and using human cells/tissue expression data to elucidate complex mechanisms driving genetic risk for JIA.

Source: medRxiv

DOI: 10.64898/2026.08.24.26361225

Authors: Kaiyu Jiang, Susan Kales, Ryan Tewhey, James N. Jarvis

Institutions: University of Washington, Jackson Laboratory

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases