Genome-wide identification and characterization of QTLs for transcriptional noise in human midbrain cells

This page provides lists of tnQTLs and eQTLs in human midbrain cells derived from iPSCs.

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 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 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 a new class of QTLs and insights into the mechanistic basis of transcriptional noise regulation and its relevance to human traits.