Interferon Signaling & Systemic Autoimmune

Intronic STAT4 tagging SNP on the primary SLE risk haplotype; the sentinel variant in studies linking STAT4 to ischemic cerebrovascular events and antiphospholipid antibody accumulation in lupus

Near-gene regulatory variant tagging an IRF5 haplotype that elevates interferon production and increases risk for lupus, systemic sclerosis, Sjögren syndrome, and seropositive rheumatoid arthritis

Intergenic regulatory variant near IFNLR1 that contacts GRHL3 via chromatin looping in keratinocytes — the C (risk) allele is associated with psoriasis susceptibility, linking type III interferon receptor signaling and epidermal barrier transcription factor control at the same locus

3'UTR variant creating a functional polyadenylation site; A allele produces a shorter, more stable IRF5 mRNA isoform driving higher IRF5 protein levels and autoimmune disease risk

A 14-bp indel 2.2 kb upstream of IRF5 that is the most strongly associated cis-regulatory variant for IRF5 expression; the deletion allele tags protective haplotypes with lower SLE susceptibility, representing the third independent cis-regulatory signal in the IRF5 5' haplotype block alongside rs13245639 and rs729302

Intronic variant in TNFSF4 that reduces OX40 ligand promoter activity and is independently associated with susceptibility to systemic sclerosis and systemic lupus erythematosus

Cis-regulatory IRF5 variant in near-perfect LD (r²=0.97) with the rs729302 protective haplotype; the T allele reduces IRF5 expression and shows allele-specific transcription factor binding in EMSA, making it a functional candidate and a high-quality WGS tag for the 5' protective haplotype block that dampens interferon-driven autoimmune susceptibility

Promoter variant in the IL-10 haplotype system — regulates IL-10 anti-inflammatory cytokine production capacity

Promoter variant affecting IL-10 production — the master anti-inflammatory cytokine that regulates immune response

Intronic IFNG variant that modulates interferon-gamma expression, with the T allele linked to elevated IFN-γ secretion, greater IBD disease severity, and altered susceptibility to tuberculosis and other immune-mediated conditions

Gain-of-function missense variant in the MDA5 viral RNA sensor, enhancing type I interferon production and increasing autoimmune disease risk

Intronic variant creating alternative splice site that increases type I interferon production and autoimmune disease risk

Tag SNP for HLA-DQ2.5 haplotype, the strongest genetic risk factor for celiac disease and associated with multiple autoimmune conditions

Upstream regulatory variant near ETV7, an interferon-inducible transcriptional repressor; the common C allele is associated with moderately increased rheumatoid arthritis risk, while the rare A allele is protective

Downstream regulatory variant in the IRF5 3' region that elevates IRF5 mRNA expression and marks the risk haplotype block associated with lupus, systemic sclerosis, and Sjögren syndrome

Intronic IL10 variant that reduces anti-inflammatory cytokine production, independently raising susceptibility to gut inflammation, H. pylori infection, and asthma severity

Downstream IL10 enhancer variant that disrupts a STAT3 binding site, reducing anti-inflammatory IL-10 production and raising susceptibility to inflammatory bowel disease, lupus, and Sjögren's syndrome

Regulatory variant in the 3′ UTR of HLA-DPA1 that controls surface expression of HLA-DP antigen-presenting molecules; G allele reduces HLA-DPA1 mRNA expression and increases susceptibility to chronic hepatitis B infection while impairing HBV vaccine antibody response

Intronic variant in the HLA class III region near MSH5 associated with lupus susceptibility, IFN-α regulation, and epistatic interactions with IRF5 and CTLA4

Intronic SKIV2L variant in the MHC class III region; the T allele tags an independent susceptibility signal for systemic lupus erythematosus separate from HLA-DRB1

Enhancer variant ~5 kb upstream of IRF5 that promotes ZBTB3-mediated chromatin looping to the IRF5 alternative promoter, driving overexpression of IRF5-short transcripts and increasing risk for lupus, Sjögren's syndrome, inflammatory bowel disease, and other autoimmune conditions; the leading causal candidate for the 5' IRF5 risk signal and a tag for the CGGGG promoter insertion that creates an extra Sp1 binding site

Regulatory tag SNP in the HLA-DRB1 region; the G allele marks the HLA-DRB1*04:01 shared epitope haplotype, conferring elevated susceptibility to anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis and accelerated joint damage progression.

MHC-region intronic variant tagging HLA-DRB1 shared epitope haplotypes; G allele is the primary GWAS signal for seropositive rheumatoid arthritis and polymyalgia rheumatica risk in Europeans

Near-gene variant tagging an IRF5 protective haplotype in the 5' promoter region that reduces type I interferon output and lowers susceptibility to lupus, rheumatoid arthritis, and related autoimmune conditions

Tag SNP identifying HLA-DQ8 haplotype, second strongest genetic risk factor for celiac disease and major type 1 diabetes risk marker

Intronic variant in TNFSF4 that tags an upstream regulatory haplotype associated with altered OX40 ligand expression, influencing T cell co-stimulation and susceptibility to autoimmune thyroid disease and viral immune responses

Intronic STAT4 variant that amplifies the interferon-alpha and IL-12 response, conferring the strongest common genetic risk for lupus outside the HLA region

Intronic tag SNP in HLA-DPB1 (and upstream of HLA-DPA1) that marks the HLA-DP haplotype controlling antigen-presenting cell surface expression; the G allele is strongly associated with chronic hepatitis B infection susceptibility and impaired hepatitis B vaccine antibody response across multiple populations

Intergenic tag SNP upstream of HLA-DRA; the G allele is the primary GWAS signal for rheumatoid arthritis susceptibility in the HLA class II region, with among the strongest effect sizes of any common RA variant (OR ~2.47 in Europeans).

3' UTR eQTL that reduces HLA-DPB1 expression, impairing antigen presentation and increasing risk for chronic hepatitis B infection; also linked to multiple sclerosis and modulates rheumatoid arthritis risk through a dose-dependent trade-off in immune activation

Regulatory variant ~15 kb upstream of IRF4 that modulates germinal center B cell differentiation and plasma cell output, associated with rheumatoid arthritis and systemic sclerosis susceptibility