Identifying genetic regulatory variants that affect transcription factor activity

Li, Xiaoting (författare): Department of Biological Sciences, Columbia University, New York, NY 10027, USA

Lappalainen, Tuuli (författare): KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,New York Genome Center, New York, NY 10013, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA

Bussemaker, Harmen J. (författare): Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA

(creator_code:org_t)

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://urn.kb.se/re...; https://doi.org/10.1...; visa färre...

Abstract Ämnesord

Stäng

Genetic variants affecting gene expression levels in humans have been mapped in the Genotype-Tissue Expression (GTEx) project. Trans-acting variants impacting many genes simultaneously through a shared transcription factor (TF) are of particular interest. Here, we developed a generalized linear model (GLM) to estimate protein-level TF activity levels in an individual-specific manner from GTEx RNA sequencing (RNA-seq) profiles. It uses observed differential gene expression after TF perturbation as a predictor and, by analyzing differential expression within pairs of neighboring genes, controls for the confounding effect of variation in chromatin state along the genome. We inferred genotype-specific activities for 55 TFs across 49 tissues. Subsequently performing genome-wide association analysis on this virtual trait revealed TF activity quantitative trait loci (aQTLs) that, as a set, are enriched for functional features. Altogether, the set of tools we introduce here highlights the potential of genetic association studies for cellular endophenotypes based on a network-based multi-omics approach. The transparent peer review record is available.

NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)

Av författaren/redakt...: Li, Xiaoting; Lappalainen, Tuu ...; Bussemaker, Harm ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

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