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Updated: Oct 26, 2025

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Cell type-specific and cross-population polygenic risk score analyses of MIR137 gene pathway in schizophrenia
Yin Yao1, Wei Guo2, Siwei Zhang3
1Department of Computational Biology, Life Science Institutes and School of Life Science and Human Phenomics Institute, Fudan University, Shanghai 200438, China.
Abstract:
Cell type-specific pathway-based polygenic risk scores (PRSs) may better inform disease biology and improve the precision of PRS-based clinical prediction. For microRNA-137 (MIR137), a leading neuropsychiatric risk gene and a post-transcriptional master regulator, we conducted a cell type-specific gene set PRS analysis in both European and Han Chinese schizophrenia (SZ) samples. We found that the PRS of neuronal MIR137 -target genes better explains SZ risk than PRS derived from MIR137 -target genes in iPSC or from the reported gene sets showing MIR137 -altered expression. Compared with the PRS derived from the whole genome or the target genes of TCF4, the PRS of neuronal MIR137 -target genes explained a disproportionally larger (relative to SNP number) SZ risk in the European sample, but with a more modest advantage in the Han Chinese sample. Our study demonstrated a cell type-specific polygenic contribution of MIR137 -target genes to SZ risk, highlighting the value of cell type-specific pathway-based PRS analysis for uncovering disease-relevant biological features.
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