Table 2

The top 16 predictors for development of IA

Selected (%)SourceFeatureFunction/description
100MetaboliteAscorbate (vitamin C)Antioxidant and coenzyme
100MetadataAge (years)Age at T1
98MetadataFirst-degree relative statusGrouped by mother with type 1 diabetes, other FDR (sibling or father), or no FDR
94Metabolite3-methyl-2-oxobutyrateBranched-chain organic acid; precursor to leucine and valine synthesis
93ProteinFCRL3 (Fc receptor-like protein 3)Promotes TLR9-induced B-cell proliferation, activation, and survival
91Metabolite4-hydroxyhippurateMicrobial end product derived from polyphenol metabolism by the microflora in the intestine
90MetadataHispanicSelf-report of Hispanic ethnicity
90ProteinNKG2D type II integral membrane protein/KLRK1 (Killer cell lectin-like receptor subfamily K member 1)Stimulatory and costimulatory innate immune response on activated killer cells; involved in immunosurveillance of virus-infected cells
89SNPrs2476601 (PTPN22)Autoimmunity gene; negative regulator of T-cell receptor signaling
89ProteinSSRP1 (Structure Specific Recognition Protein 1)/FACT (Facilitates Chromatin Transcription) complex subunitThe FACT complex plays a role in mRNA elongation, DNA replication, and DNA repair
89MetabolitePyroglutamineGlutamine and glutathione metabolism
87ProteinMMP-2Metalloproteinase involved in diverse functions including angiogenesis, tissue repair, and inflammation
86ProteinActivin AMember of TGF-β superfamily of cytokines; plays role in regulation of tissue homeostasis, organ development, inflammation, cell proliferation, and apoptosis
85SNPrs2476601 (PTPN22)Autoimmunity gene; negative regulator of T-cell receptor signaling
84ProteinCSK21 (Casein kinase II subunit alpha)Regulates various cellular processes including cell cycle progression, apoptosis, and transcription as well as response to viral infections
84SNPrs3087243 (CTLA4)Autoimmunity gene; negative regulator of T-cell responses
  • Analysis by ROFI-P3 comparing control subjects with pooled antibody-positive subjects and subjects with type 1 diabetes. Ranking by selection frequency for metabolites and proteins (fold change from T1 to T2) or SNPs (risk allele count). Proteins: www.genecards.org and www.uniprot.org. SNPs: www.SNPedia.com. Metabolite: www.hmdb.ca.