文章基本信息

标题：Cell type-specific and cross-population polygenic risk score analyses of MIR137 gene pathway in schizophrenia
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作者：Yin Yao ; Wei Guo ; Siwei Zhang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：7
页码：1-18
DOI：10.1016/j.isci.2021.102785
语种：English
出版社：Elsevier
摘要：SummaryCell type-specific pathway-based polygenic risk scores (PRSs) may better inform disease biology and improve the precision of PRS-based clinical prediction. FormicroRNA-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 neuronalMIR137-target genes better explains SZ risk than PRS derived fromMIR137-target genes in iPSC or from the reported gene sets showingMIR137-altered expression. Compared with the PRS derived from the whole genome or the target genes ofTCF4, the PRS of neuronalMIR137-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 ofMIR137-target genes to SZ risk, highlighting the value of cell type-specific pathway-based PRS analysis for uncovering disease-relevant biological features.Graphical abstractDisplay OmittedHighlights•PRS of neuralMIR137target genes better explains schizophrenia (SZ) risk variance•SZ risk and SNP heritability explained byMIR137target genes is cell type-specific•MIR137target genes explain a disproportionally larger SZ risk than genomic control•PRS ofMIR137target genes better explains SZ risk in Europeans than in Han ChineseBiological sciences; Genomics; Neuroscience