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

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.