Psoriasis & Spondyloarthropathy

Upstream tagging SNP at the IL12B locus; the C allele is associated with increased susceptibility to psoriasis and other IL-12/IL-23-mediated autoimmune conditions

Missense variant (Asp575Asn) in ERAP1; 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)

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

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 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 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, 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 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 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

Regulatory variant upstream of IL12B associated with increased risk of multiple sclerosis, psoriasis, and primary biliary cholangitis

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

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 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)

Intronic variant in IKBKE (IKK-epsilon) associated with psoriasis susceptibility; the T allele modestly increases risk

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

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

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