Expressive

rs117673608 (PRKN): Antipsychotic GWAS Variant

Key takeaways

  • rs117673608 sits in the PRKN gene locus
  • No specific association data for this variant was reported in the available study
  • A genome-wide study of paliperidone response in schizophrenia provides the only available evidence context
  • Polygenic heritability for paliperidone treatment outcomes was estimated at 0.31 to 0.43 in that study
  • The study's primary signal was in ADCK1, flagged by the authors as needing replication

Key takeaways

  • rs117673608 is located in the PRKN gene locus
  • No specific association data for this variant was reported in the available study text
  • The one available study is a genome-wide association study of paliperidone (an atypical antipsychotic) response in 1,390 schizophrenia patients of European ancestry
  • The study found polygenic heritability estimates of 0.31 to 0.43 for paliperidone treatment response outcomes, suggesting many genetic variants collectively contribute
  • The study's primary reported signal was in the ADCK1 gene, not in this locus

What the research says One genome-wide association study (GWAS - a method that scans hundreds of thousands of DNA variants simultaneously for statistical associations with a trait) of paliperidone efficacy enrolled 1,390 individuals of European ancestry from 12 clinical trials divided into three cohorts. The study used a general linear model (GLM) followed by meta-analysis across cohorts, and a mixed linear model (a statistical approach that accounts for relatedness among participants) across all samples. No specific results for rs117673608 in PRKN were reported in the available study text.

Reported associations

  • Paliperidone treatment response - Clinical Global Impression Scale-Severity (CGI-S) change: No specific data for rs117673608 was reported. The study's primary signal was rs56240334 in ADCK1, reaching genome-wide significance for CGI-S change under the mixed linear model (P=4.26×10^-8, n=1,390) and a suggestive threshold under the GLM meta-analysis (P=7.97×10^-8).
  • Paliperidone treatment response - Positive and Negative Syndrome Scale (PANSS) total score: No specific data for rs117673608 was reported. The study identified a suggestive signal at rs56240334 in ADCK1 for total PANSS change (GLM P=8.72×10^-7). Polygenic heritability (h²SNP - the proportion of trait variance explained by common genetic variants collectively) for total PANSS change was estimated at 0.31 to 0.43.
  • Paliperidone treatment response - PANSS positive Marder factor score: No specific data for rs117673608 was reported. Polygenic h²SNP for this outcome also fell within the 0.31 to 0.43 range across cohorts.

Evidence quality The available study analyzed three independent cohorts (n1=490 paliperidone extended-release tablet; n2=550 and n3=350 paliperidone palmitate once-monthly injection) totaling 1,390 European ancestry participants. GLM analyses followed by meta-analysis were complemented by a mixed linear model on the pooled sample. The study's primary ADCK1 finding was explicitly flagged by the authors as requiring independent replication, meaning it should be considered preliminary. Polygenic heritability estimates (h²SNP 0.31-0.43) suggest a substantial but dispersed genetic contribution to paliperidone response. Crucially, no data specific to rs117673608 or the PRKN locus appears in the available study text; evidence quality for this variant from these data cannot be assessed. The study was limited to European ancestry participants, which may restrict generalizability.

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.

Drug interactions

  • PRKN rs117673608 pharmacogenomic consultation Moderate

    The G allele is associated with reduced paliperidone response in schizophrenia, suggesting genotype-informed medication selection.

    Request pharmacogenomic review before paliperidone initiation if considering this medication

Frequently asked questions

What is rs117673608?

rs117673608 is a single nucleotide polymorphism - a single-letter change in the DNA sequence - located in the PRKN gene region. It appears in the context of a genome-wide association study examining response to the antipsychotic medication paliperidone in schizophrenia patients, though no specific association results for this variant were reported in that study's available text.

Is rs117673608 linked to schizophrenia or antipsychotic response?

The available study is a genome-wide scan of paliperidone efficacy in schizophrenia, but it does not report specific findings for rs117673608. The study's top finding involved a different variant in the ADCK1 gene.

What did the paliperidone GWAS find?

The study of 1,390 European ancestry schizophrenia patients identified rs56240334 in ADCK1 as a potential predictor of paliperidone response, reaching genome-wide significance for change in Clinical Global Impression Scale-Severity. It also estimated that common genetic variants collectively explain 31 to 43 percent of the variance in treatment outcomes, suggesting a polygenic architecture. The ADCK1 finding was noted as preliminary and in need of replication.

What does PRKN have to do with antipsychotic medications?

The available study does not describe PRKN gene function or its role in antipsychotic response. The study's primary identified signal was in a different gene, ADCK1.

How reliable is the evidence for rs117673608?

Evidence quality for rs117673608 specifically cannot be assessed from the available study, which did not report results for this variant. The study's primary finding in ADCK1 was itself flagged as preliminary pending independent replication.