biostudies-literatureUnknownLiu LNCATS NIH HHSNIDDK NIH HHSNIAID NIH HHSNCI NIH HHSNIGMS NIH HHSIgA 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 <i>HLA</i>-<i>DRB1</i> (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: <i>FCAR</i> (OR=1.51, P=1.0×10^-20) encoding a myeloid IgA receptor FcαR, and <i>INPP5D</i> (OR=1.34, P=2.2×10^-9) encoding a knownmedRxiv : the preprint server for health sciences2024.10.10.24315041https://www.ebi.ac.uk/biostudies/studies/S-EPMC11482997biostudies-literatureGenome-wide studies define new genetic mechanisms of IgA vasculitis.PMC11482997UL1 TR002384R01 DK082753R01 DK105124R35 CA197745K01 DK137031R01 DK078244RC2 DK116690T32 GM007367R01 AI149431F30 CA257765R56 DK078244Zanoni FRizk DLugani FVasylyeva TLBadenski AZhang HGriffin ASamsonov DJankauskiene ALundberg SSiniewiczLuzenczyk KGonzalez-Gay MAMartin JKiryluk KBiancone LSmoyer WEMachura EMahan JDBerthelot LBomback ASKottgen AHastings MCVogt BMiklaszewska MPillebout EFlorczak MNelson RAl-Akash SIorember FKaminska DSikora PWeng PDavis TKHryszko TSelewski DZaniew MCalifano ANovak JLin FForoncewicz BKallash MGradzinska AScolari FSilva CLiu LMonteiro RCGreen TJEsposito VMaterna-Kiryluk ARanch DMatar RBMizerska-Wasiak MTesar VQuiroga AChishti AMarasa MSreedharan RKrakowczyk HZhang JYAppel GBClaes DFlynn JTPawlaczyk KMani LYCaliskan YAkchurin OVlahos LJEsposito CGharavi AGBerrouet CMason SDe Jager PLFujita MJulian BARheault MNIzzi CZhou XJOlszewska MPaczek LKwella NMonteiro-Martins SHidalgo GWenderfer SWyatt RJSzczepanska MXiao NAmoroso ABono LMucha KDrozdz DZhu LZaza GBodria MfalseGenome-wide studies define new genetic mechanisms of IgA vasculitis.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 <i>HLA</i>-<i>DRB1</i> (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: <i>FCAR</i> (OR=1.51, P=1.0×10^-20) encoding a myeloid IgA receptor FcαR, and <i>INPP5D</i> (OR=1.34, P=2.2×10^-9) encoding a known2024-01-01T00:00:00Z2024 Oct2026-05-28T03:12:45.43Z2025-04-06T22:43:14.76ZS-EPMC114829973941713310.1101/2024.10.10.24315041