2026-04-09 理化学研究所,,大阪大学,東京大学大学院総合文化研究科
本研究の概要図
＜関連情報＞
- https://www.riken.jp/press/2026/20260409_2/index.html
- https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00229-9
ヒト中脳細胞における転写ノイズに関するQTLのゲノムワイドな同定と特徴付け Genome-wide identification and characterization of QTLs for transcriptional noise in human midbrain cells
Naoki Hirose ∙ Shota Mizuno ∙ Yuki Niwa ∙ … ∙ Junko Ueda ∙ Takashi Tsuboi ∙ Atsushi Takata
Cell Reports Published:March 26, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.117151
Highlights
- Genetic loci associated with transcriptional noise were mapped genome wide
- tnQTLs exhibit effects that are more specific to cellular conditions than eQTLs
- tnQTLs without eQTL effects are enriched in distinct genomic annotations
- Schizophrenia patient and model brains show dysregulated transcriptional noise
Summary
While cell-to-cell variation in gene expression, also known as “transcriptional noise,” plays various biological roles, its regulation by genetic variants remains elusive. To address this, we analyzed single-cell RNA sequencing (scRNA-seq) data of induced pluripotent stem cell-derived midbrain cells from 155 individuals together with their genotypes and identified significant quantitative trait loci for transcriptional noise (tnQTLs) genome wide. Among these, tnQTLs without significant effects on expression abundance (termed tn>eQTLs) exhibited characteristics such as drastic alterations under oxidative stress. Analyses using genome-wide association study (GWAS) summary statistics identified enrichment of schizophrenia association signals in tn>eQTLs, as well as putative causal effects of transcriptional noise dysregulation in specific genes. We also analyzed brain scRNA-seq data for schizophrenia and found marked disease-associated transcriptional noise alterations in superficial- and deep-layer excitatory neurons. Overall, this study provides a resource for tnQTLs and insights into the mechanistic basis of transcriptional noise regulation and its relevance to human traits.
