Psoriasis & Spondyloarthropathy

Upstream tagging SNP at the IL12B locus that marks the Th1/Th17 risk haplotype; the C allele is associated with elevated IL-12p40 expression and increased susceptibility to psoriasis, Crohn's disease, and other IL-12/IL-23-mediated autoimmune conditions

Missense variant (Asp575Asn) in the ERAP1 catalytic domain that modestly reduces peptide trimming efficiency; the protective T allele (Asn575) is co-protective with rs30187 Arg528, with combined homozygous protective state conferring 3-4x lower ankylosing spondylitis risk in HLA-B27-positive individuals

Missense variant in the keratinocyte NF-κB scaffold protein CARD14 that modestly elevates psoriasis susceptibility and strongly predicts favorable response to anti-TNF biologic therapy (adalimumab, etanercept, infliximab)

Near-gene variant at the IL12B locus associated with psoriasis risk through altered expression of the p40 subunit shared by IL-12 and IL-23 cytokines

Tag SNP for HLA-C*06:02, the strongest genetic risk factor for psoriasis, determining disease phenotype and predicting differential response to biologic therapy

Regulatory variant near NFKBIA that specifically elevates risk for psoriatic arthritis over skin-only psoriasis, enabling early PsA risk stratification in people with psoriasis before irreversible joint damage occurs

Missense variant in the IL-17 adaptor Act1 (Arg74Trp) that is the primary GWAS hit for psoriatic arthritis at the TRAF3IP2 locus (OR=1.83, P=8.56×10⁻¹⁷); in strong LD with the functional D10N variant but appears to tag a partially overlapping, PsA-enriched haplotype

Intronic variant near the TRAF3IP2 locus (annotated in IPCEF1 at chr6q25.2 by dbSNP, 43 Mb distal) that was genotyped alongside TRAF3IP2 coding variants in SLE studies; the A allele is independently associated with SLE susceptibility (OR=1.73, P=0.046) and SLE pericarditis in the Ciccacci 2013 Italian cohort — completing the three-SNP TRAF3IP2/locus panel

Intronic tagging variant in the TRAF3IP2/TRAF3IP2-AS1 locus that distinguishes two independent psoriasis risk haplotypes; the minor A allele marks a secondary haplotype (OR=1.8 for psoriasis) while the common G allele co-segregates with the primary D10N risk haplotype (OR=2.7); together the four-SNP set provides full haplotype coverage at this IL-17 adaptor locus

Intronic variant in the TRAF3IP2 locus that lies within the antisense lncRNA TRAF3IP2-AS1 and amplifies IL-17 pathway dysregulation; the G allele is a gain-of-function mutation enhancing SRSF10 recruitment that suppresses IRF1-driven Act1 transcription; the G allele independently associates with psoriasis (OR=1.69) and co-occurs on a secondary risk haplotype (OR=1.8) alongside the primary risk haplotype carrying rs13210247_A (OR=2.7)

Synonymous coding variant in exon 4 of IKBKE (IKK-epsilon); the C allele tags an IKBKE haplotype associated with increased SLE susceptibility through dysregulated type I interferon signaling, and has been implicated in antiviral innate immunity

Missense variant (Arg725Gln) in the ERAP1 peptide-binding domain that reduces aminopeptidase activity; the T allele tags the low-activity Hap10 haplotype, which is protective against ankylosing spondylitis and psoriasis but recessively increases Behçet's disease risk — especially in HLA-B*51 carriers

Intergenic regulatory variant near TNIP1 whose A allele reduces ABIN1-mediated NF-kB braking, conferring OR=1.69 for psoriasis per allele and substantially elevated generalized pustular psoriasis risk in homozygous carriers

Intronic variant near IL23A encoding the IL-23 p19 subunit; G allele increases psoriasis and psoriatic arthritis risk through elevated IL-23 signalling and Th17 activation

Intronic variant in the IL-23 receptor gene associated with increased risk of psoriasis, psoriatic arthritis, Crohn's disease, and ankylosing spondylitis through altered IL-23 signaling and Th17 cell activation

Synonymous coding variant in the lymphotoxin-beta receptor gene associated with altered LTBR signaling capacity and susceptibility to IgA nephropathy; the LTBR locus on chromosome 12p13 is independently implicated in ankylosing spondylitis at genome-wide significance

Regulatory variant upstream of IL12B associated with increased risk of multiple sclerosis, psoriasis, and primary biliary cholangitis through altered IL-12/IL-23 cytokine expression

Missense variant (Arg127Pro) in ERAP1 that subtly alters ER peptide trimming kinetics, increasing autoimmune risk for psoriasis and ankylosing spondylitis particularly in individuals carrying HLA-C*06:02 or HLA-B27; association is strongest for disease onset in adolescence

Missense variant in the ERAP1 C-terminal regulatory domain modulating peptide trimming length-selectivity; Gln730 (G allele, risk) is part of hyperactive ERAP1 haplotypes that over-trim peptides for HLA class I presentation, increasing ankylosing spondylitis susceptibility in HLA-B27 carriers

Intronic ERAP1 variant that increases expression, raising psoriasis risk specifically in HLA-C*06:02 carriers through enhanced autoantigen trimming

Missense variant reducing ERAP1 aminopeptidase activity, increasing ankylosing spondylitis and psoriasis risk through altered MHC class I peptide trimming — effect contingent on HLA-B27 and HLA-C*06:02 carrier status

IL12B 3'-UTR variant forming the canonical two-SNP psoriasis risk haplotype with rs6887695; T allele (coding-strand A, risk) drives 12.5-fold higher IL12B expression and substantially elevated psoriasis susceptibility; G allele is protective and predicts better ustekinumab response

Intronic IL12B variant in linkage with the promoter-regulatory haplotype; T allele is protective against psoriasis and associated with better ustekinumab (anti-p40) response

Missense variant in Act1 that abolishes IL-17 signaling by disrupting TRAF6 binding, driving paradoxical hyperactivation of Th17 responses and psoriasis susceptibility

Intronic variant in the GPX3/TNIP1 regulatory locus on chromosome 5; the C allele is protective against generalized pustular psoriasis (OR≈0.61 per C allele) by tagging a haplotype associated with maintained ABIN-1/NF-κB regulatory capacity

Intronic variant in IKBKE (IKK-epsilon) associated with psoriasis susceptibility; the T allele modestly increases risk by influencing the dual NF-kB/type I interferon signaling node encoded by this kinase

Intronic tag SNP located 41 kb centromeric of HLA-B and 5.4 kb telomeric of MICA; the A allele tags HLA-B*27:05 and related European HLA-B27 subtypes with 98% sensitivity and 99% specificity, serving as a genetic proxy for HLA-B27 status and enabling contextualization of ERAP1 × HLA-B27 epistasis in ankylosing spondylitis risk

Near-HLA-C intergenic variant that tags HLA-C*06:02 haplotype, conferring risk for early-onset psoriasis vulgaris through MHC class I antigen presentation

Intronic regulatory variant in TNFAIP3 — the primary NF-kB brake gene — with the C allele independently increasing psoriasis susceptibility (OR 1.23) and showing pleiotropic associations across multiple autoimmune conditions

Intronic variant in TNFAIP3 whose G allele is the primary psoriasis susceptibility signal at 6q23.3, tagging a regulatory haplotype distinct from the rheumatoid arthritis and lupus signals at the same locus, and predicting better response to TNF inhibitor therapy

Rare missense variant in the keratinocyte NF-κB scaffold protein CARD14 that may predict favorable response to anti-TNF biologic therapy in psoriasis patients

Upstream regulatory variant ~60 kb 5' of IL12B, forming the canonical two-SNP psoriasis risk haplotype with rs3212227 (3'-UTR); C allele elevates IL-12/IL-23 p40 expression, increasing psoriasis, psoriatic arthritis, and IBD susceptibility

Regulatory variant upstream of NFKBIA that specifically elevates risk of psoriatic arthritis over skin-only psoriasis, with a 3.2-fold odds ratio distinguishing arthritic from cutaneous-only disease in psoriasis patients

Intronic variant in the interferon lambda receptor 1 gene that elevates PsA risk by amplifying IL-29/IFN-lambda signaling in synovial tissue, marking those with skin psoriasis who are at elevated risk for progressing to joint disease

Intergenic variant near the IL23A locus associated with psoriasis and psoriatic arthritis susceptibility through the IL-23/Th17 inflammatory axis