{"entity": "publication", "iuid": "45ed0e7d11e64d6f8393598672f64147", "timestamp": "2026-08-20T21:34:40.626Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/45ed0e7d11e64d6f8393598672f64147.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/45ed0e7d11e64d6f8393598672f64147"}}, "title": "Identifying genetic regulatory variants that affect transcription factor activity.", "authors": [{"family": "Li", "given": "Xiaoting", "initials": "X"}, {"family": "Lappalainen", "given": "Tuuli", "initials": "T"}, {"family": "Bussemaker", "given": "Harmen J", "initials": "HJ"}], "type": "journal article", "published": "2023-09-13", "journal": {"title": "Cell Genom", "issn": "2666-979X", "volume": "3", "issue": "9", "pages": "100382", "issn-l": null}, "abstract": "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.", "doi": "10.1016/j.xgen.2023.100382", "pmid": "37719147", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10504674"}, {"db": "pii", "key": "S2666-979X(23)00179-9"}], "notes": [], "created": "2026-08-20T08:06:31.827Z", "modified": "2026-08-20T08:06:31.882Z"}