Genetic effects on promoter usage are highly context-specific and contribute to complex traits.
Kaur Alasoo,Julia Rodrigues,John Danesh,Daniel F. Freitag,Daniel F. Freitag,Dirk S. Paul,Dirk S. Paul,Daniel J. Gaffney +7 more
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TLDR
It is found that promoters, splicing and 3ʹ ends were predominantly controlled by independent genetic variants enriched in distinct genomic features, suggesting promoter usage might be an underappreciated molecular mechanism mediating complex trait associations in a context-specific manner.Abstract:
Genetic variants regulating RNA splicing and transcript usage have been implicated in both common and rare diseases. Although transcript usage quantitative trait loci (tuQTLs) have been mapped across multiple cell types and contexts, it is challenging to distinguish between the main molecular mechanisms controlling transcript usage: promoter choice, splicing and 3' end choice. Here, we analysed RNA-seq data from human macrophages exposed to three inflammatory and one metabolic stimulus. In addition to conventional gene-level and transcript-level analyses, we also directly quantified promoter usage, splicing and 3' end usage. We found that promoters, splicing and 3' ends were predominantly controlled by independent genetic variants enriched in distinct genomic features. Promoter usage QTLs were also 50% more likely to be context-specific than other tuQTLs and constituted 25% of the transcript-level colocalisations with complex traits. Thus, promoter usage might be an underappreciated molecular mechanism mediating complex trait associations in a context-specific manner.read more
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Mapping of promoter usage QTL using RNA-seq data reveals their contributions to complex traits
Naoto Kubota,Mikita Suyama +1 more
TL;DR: A computational framework for identifying genomic loci associated with promoter activities, called promoter usage quantitative trait loci (puQTL), using conventional RNA-seq data is proposed and most puQTL signals were concordant with at least one genome-wide association study (GWAS) signal, enabling novel interpretations of the molecular mechanisms of complex traits.
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Transcriptome and chromatin accessibility landscapes across 25 distinct human brain regions expand the susceptibility gene set for neuropsychiatric disorders
Pengfei Dong,Jaroslav Bendl,Ruth Misir,Zhiping Shao,Jonathan Edelstien,David A. Davis,Vahram Haroutunian,William K. Scott,Susanne Acker,Nathan Lawless,Gabriel E. Hoffman,John F. Fullard,Panos Roussos +12 more
TL;DR: An atlas of chromatin accessibility and gene expression in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls is provided, providing a valuable resource for studying molecular regulation across multiple regions of the human brain.
Journal ArticleDOI
Clinical traits impacting human tissue transcriptomes
TL;DR: Garcia-Perez et al. as discussed by the authors performed a comprehensive association analysis between gene expression and splicing measured by the GTEx Consortium in 46 human tissues and 21 demographic and clinical traits.
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Detecting isoform-level allelic imbalance accounting for inferential uncertainty
TL;DR: SEESAW as discussed by the authors uses the TSS-based aggregation strategy to identify transcripts with high IU with respect to allelic quantification, which can be applied in a paired setting to detect AI.
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Quantifying transcriptome diversity: a review.
TL;DR: In this article , a comprehensive overview of how gene expression diversity arises, and how measuring it determines a more complete picture of heterogeneity across proteins, cells, tissues, organisms and species is provided.
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