rs10782001 (FBXL19): Psoriasis Risk Variant

Key takeaways

• rs10782001 near FBXL19 reached genome-wide significance for psoriasis in a study combining roughly 5,900 cases and 7,200 controls across discovery and replication cohorts
• The variant is linked to both psoriatic arthritis (joint-involving) and purely cutaneous (skin-only) forms of psoriasis
• GTEx data show the alternate allele reduces expression of multiple genes in skin, nerve, muscle, and thyroid
• The association was independently replicated in cohorts from North America and Europe
• No lifestyle factors have been directly linked to this variant in the available literature

What the research says A meta-analysis of two genome-wide association studies, followed by three stages of independent replication in cohorts from Michigan, Toronto, Newfoundland, and Germany, identified rs10782001 near FBXL19 as a psoriasis susceptibility locus at combined p = 9 x 10^-10 across approximately 5,895 cases and 7,231 controls PMID 20953186. The same locus was strongly associated with both the psoriatic arthritis subphenotype and purely cutaneous psoriasis within that analysis PMID 20953186. A broader genome-wide analysis of more than 19,000 individuals comparing atopic dermatitis and psoriasis found no evidence for shared loci acting in the same direction on both conditions, consistent with these diseases being driven by opposing genetic mechanisms PMID 26637977.

Reported associations

• Psoriasis vulgaris: genome-wide significant association (p = 9 x 10^-10) in combined discovery and replication samples of approximately 5,895 cases and 7,231 controls drawn from North America and Europe PMID 20953186
• Psoriatic arthritis (subphenotype): strong association with this joint-involving form of psoriasis, assessed as a subphenotype within the same multi-cohort study PMID 20953186
• Purely cutaneous psoriasis (subphenotype): strong association with the skin-only form, showing the locus is not restricted to the arthritis subtype PMID 20953186

Evidence quality The association at rs10782001 surpassed the conventional genome-wide significance threshold (p < 5 x 10^-8), achieving a combined p = 9 x 10^-10 across a discovery phase (1,831 cases, 2,546 controls) and up to three independent replication stages totaling 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland, and Germany PMID 20953186. The multi-stage design with geographically diverse cohorts strengthens confidence in this finding; however, no odds ratio or beta coefficient for rs10782001 is reported in the available study text, limiting direct comparison of effect magnitude. No conflicting findings regarding this locus appear in the available studies. A comparative analysis of atopic dermatitis and psoriasis in more than 19,000 individuals found no evidence of loci operating in the same direction on both conditions, supporting the disease-specificity of the FBXL19 susceptibility signal PMID 26637977.

Tissue-specific expression effects eQTL associations below describe links between rs10782001 and gene expression levels in specific tissues; they reflect biological mechanism rather than clinical outcomes.

• ENSG00000260911: the alternate allele is associated with reduced expression in non-sun-exposed skin (suprapubic), tibial nerve, and subcutaneous adipose tissue GTEx Portal
• HSD3B7: the alternate allele is associated with reduced expression in skeletal muscle, sun-exposed skin of the lower leg, esophageal mucosa, and non-sun-exposed skin GTEx Portal
• STX1B: the alternate allele is associated with reduced expression in thyroid tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.