Expressive

rs10220768 (PWRN4): Psoriasis Anti-TNF Response

Key takeaways

  • rs10220768 was associated with approximately 5.5-fold higher odds of achieving a 75% or greater reduction in psoriasis severity on etanercept therapy
  • The variant is located near NPAP1 and PWRN4 on chromosome 15q11.2, one of seven loci identified in a Chinese psoriasis GWAS meta-analysis
  • Evidence comes from a single meta-analysis of 177 Chinese patients and has not been independently replicated
  • GTEx data shows the alternate allele is linked to increased PWRN4 expression in two basal ganglia brain regions
  • These findings are preliminary and require further validation before conclusions can be drawn

Key takeaways

  • rs10220768 was associated with approximately 5.5-fold higher odds of achieving a 75% or greater reduction in psoriasis severity on etanercept therapy
  • The variant is located near NPAP1 and PWRN4 on chromosome 15q11.2, one of seven loci identified in a Chinese psoriasis GWAS meta-analysis
  • Evidence comes from a single meta-analysis of 177 Chinese patients and has not been independently replicated
  • GTEx data shows the alternate allele is linked to increased PWRN4 expression in two basal ganglia brain regions
  • These findings are preliminary and require further validation before conclusions can be drawn

What the research says A meta-analysis of two independent Chinese psoriasis cohorts identified rs10220768 - annotated to NPAP1 on chromosome 15q11.2, a region that also contains PWRN4 - as one of seven loci associated with response to etanercept biosimilar treatment. The alternate allele reached an odds ratio of 5.49 (p = 1.48 × 10^-6), meaning carriers were over five times more likely to achieve PASI-75 (a 75% improvement in psoriasis area and severity index) after 24 weeks. This variant was also among six of the seven identified SNPs reported to show significant eQTL effects (p < 1 × 10^-6) across multiple tissues.

Reported associations

  • Anti-TNF-α treatment response (psoriasis): The alternate allele was associated with good response to etanercept biosimilar (PASI improvement ≥75% at 24 weeks), with an odds ratio of 5.49 (p = 1.48 × 10^-6) in a meta-analysis of 177 Chinese patients (148 good responders, 29 poor responders)

Evidence quality The sole study reporting this association combined two small independent Chinese cohorts into a meta-analysis (total n = 177 evaluable participants - 148 good responders and 29 poor responders - drawn from 212 enrolled patients). The locus reached p < 10^-5 but did not achieve conventional genome-wide significance (p < 5 × 10^-8). No independent replication cohort was available, and the authors explicitly state these results require further validation. The sample is restricted to Chinese Han patients receiving a specific etanercept biosimilar regimen, which limits generalizability to other ancestries or TNF-α inhibitor agents. There are no conflicting studies in the provided data, but the small sample size and absence of replication make this evidence preliminary.

Tissue-specific expression effects

  • PWRN4: The alternate allele at rs10220768 is associated with increased expression of PWRN4 (ENSG00000304107) in the nucleus accumbens (basal ganglia) and putamen (basal ganglia) GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Lifestyle context

Concrete actions anchored to the cited research. We do not prescribe, we describe.

Discuss with your doctor

  • anti-TNF therapy response based on rs10220768 Moderate

    rs10220768 in PWRN4 is associated with response to anti-TNF-alpha inhibitors in psoriasis through effects on NPAP1 gene expression

    Discuss genotype with dermatologist or rheumatologist before starting anti-TNF therapy

Frequently asked questions

What is rs10220768?

rs10220768 is a single nucleotide polymorphism located near the NPAP1 and PWRN4 genes on chromosome 15q11.2. A GWAS meta-analysis identified it as one of seven loci potentially associated with how well Chinese psoriasis patients respond to etanercept, a TNF-α inhibitor biologic drug.

Is rs10220768 linked to psoriasis treatment response?

One meta-analysis of two small Chinese cohorts found the alternate allele of rs10220768 was associated with approximately 5.5-fold higher odds of achieving strong response - 75% or greater improvement in psoriasis severity - to etanercept biosimilar therapy. The finding is preliminary and has not been independently replicated.

What genes are near rs10220768?

The GWAS study annotated rs10220768 to NPAP1 on chromosome 15q11.2. GTEx data also links this variant to expression of PWRN4 (ENSG00000304107), another gene in the same chromosomal region.

Does rs10220768 affect gene expression in the brain?

According to GTEx v11 data, the alternate allele at rs10220768 is associated with increased expression of PWRN4 in the nucleus accumbens and putamen, two structures within the basal ganglia. The clinical significance of this expression effect is not established.

How strong is the evidence for rs10220768?

The evidence is preliminary. The association comes from a single meta-analysis of 177 Chinese patients that reached p = 1.48 × 10^-6 but did not meet conventional genome-wide significance. No independent replication cohort was available, and the study authors explicitly call for further validation.