Genome-wide studies define new genetic mechanisms of IgA vasculitis.

ABSTRACT: IgA vasculitis (IgAV) is a pediatric disease with skin and systemic manifestations. Here, we conducted genome, transcriptome, and proteome-wide association studies in 2,170 IgAV cases and 5,928 controls, generated IgAV-specific maps of gene expression and splicing from blood of 255 pediatric cases, and reconstructed myeloid-specific regulatory networks to define disease master regulators modulated by the newly identified disease driver genes. We observed significant association at the HLA-DRB1 (OR=1.55, P=1.1×10^-25) and fine-mapped specific amino-acid risk substitutions in DRβ1. We discovered two novel non-HLA loci: FCAR (OR=1.51, P=1.0×10^-20) encoding a myeloid IgA receptor FcαR, and INPP5D (OR=1.34, P=2.2×10^-9) encoding a known

SUBMITTER: Liu L 

PROVIDER: S-EPMC11482997 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature