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Identifying genetic...
Identifying genetic regulatory variants that affect transcription factor activity
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- Li, Xiaoting (author)
- Department of Biological Sciences, Columbia University, New York, NY 10027, USA
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- Lappalainen, Tuuli (author)
- 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
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- Bussemaker, Harmen J. (author)
- Department of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 3:9
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- 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)
Keyword
- aQTL
- beta-binomial distribution
- gene regulation
- generalized linear model
- genetic variation
- genome-wide association
- quantitative trait locus
- RNA-seq data
- trans-acting genetic variation
- transcription factor activity
- transcription factor perturbation signatures
Publication and Content Type
- ref (subject category)
- art (subject category)
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