rs10766681 (PRMT3): Risperidone Response in Schizophrenia

Key takeaways

• rs10766681 is a variant in or near PRMT3, identified in a pharmacogenomics study of how patients with schizophrenia respond to risperidone treatment.
• The study combined genome-wide association study (GWAS) and whole exome sequencing (WES) methods across multiple clinical centers in China.
• Treatment response was assessed in 189 patients (GWAS arm) and 222 patients (WES arm) after eight weeks of risperidone treatment using the Positive and Negative Syndrome Scale (PANSS).
• Evidence is preliminary: the study used a relatively small, single-ethnicity sample and independent replication has not been described in the available study text.
• Specific effect sizes for rs10766681 are not reported in the available study excerpt.

What the research says A multicenter pharmacogenomic study enrolled patients with schizophrenia at multiple centers across China and applied both GWAS (n = 189) and WES (n = 222) to examine the genetic basis of risperidone treatment response, where risperidone is a widely prescribed antipsychotic medication. Response was quantified as percentage change on the PANSS (Positive and Negative Syndrome Scale, a standardized clinical rating tool that covers positive symptoms such as hallucinations, negative symptoms such as social withdrawal, and cognitive symptoms) after eight weeks of treatment. Association signals across the study tended to cluster within the GPCR (G protein-coupled receptor) gene family and GPCR signaling pathway, and no loci were shared between the GWAS and WES arms.

Reported associations

• Risperidone treatment response in schizophrenia: rs10766681, located in or near PRMT3 (Protein Arginine Methyltransferase 3, an enzyme that modifies proteins by adding methyl chemical groups), was identified in the context of a pharmacogenomics GWAS of antipsychotic treatment response in a Chinese cohort. Specific effect sizes for this variant are not provided in the available study text.

Evidence quality The source study used a joint GWAS and WES design across multiple centers in China, with 189 patients in the GWAS arm and 222 in the WES arm. These are relatively small samples by current pharmacogenomics standards, which typically require thousands of participants for robust, replicable findings. The antipsychotic response phenotype was measured as percentage change on PANSS after eight weeks, a clinically validated but composite measure. The study authors themselves note that even well-powered GWAS studies tend to identify loci explaining only a small proportion of genetic variance for antipsychotic treatment response, reflecting a recognized challenge in this field sometimes called the missing heritability problem. The entire cohort is drawn from a Chinese population, which limits generalizability to other ethnic groups. No replication in independent cohorts is described in the available text, no p-value or effect size for rs10766681 specifically is present in the provided excerpt, and the finding should be considered preliminary until confirmed in larger, more diverse samples.

Lifestyle considerations No lifestyle considerations on file for this variant.