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Flynn, E. D.
(författare)
Transcription factor regulation of eQTL activity across individuals and tissues
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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2022-01-31
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Public Library of Science (PLoS),2022
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-320335
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-320335URI
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https://doi.org/10.1371/journal.pgen.1009719DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20230215
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Tens of thousands of genetic variants associated with gene expression (cis-eQTLs) have been discovered in the human population. These eQTLs are active in various tissues and contexts, but the molecular mechanisms of eQTL variability are poorly understood, hindering our understanding of genetic regulation across biological contexts. Since many eQTLs are believed to act by altering transcription factor (TF) binding affinity, we hypothesized that analyzing eQTL effect size as a function of TF level may allow discovery of mechanisms of eQTL variability. Using GTEx Consortium eQTL data from 49 tissues, we analyzed the interaction between eQTL effect size and TF level across tissues and across individuals within specific tissues and generated a list of 10,098 TF-eQTL interactions across 2,136 genes that are supported by at least two lines of evidence. These TF-eQTLs were enriched for various TF binding measures, supporting with orthogonal evidence that these eQTLs are regulated by the implicated TFs. We also found that our TF-eQTLs tend to overlap genes with gene-by-environment regulatory effects and to colocalize with GWAS loci, implying that our approach can help to elucidate mechanisms of context-specificity and trait associations. Finally, we highlight an interesting example of IKZF1 TF regulation of an APBB1IP gene eQTL that colocalizes with a GWAS signal for blood cell traits. Together, our findings provide candidate TF mechanisms for a large number of eQTLs and offer a generalizable approach for researchers to discover TF regulators of genetic variant effects in additional QTL datasets.
Ämnesord och genrebeteckningar
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NATURVETENSKAP Biologi Genetik hsv//swe
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NATURAL SCIENCES Biological Sciences Genetics hsv//eng
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interferon regulatory factor 1
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IRF1 protein
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human
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transcription factor
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allele
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binding site
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biological model
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gene knockdown
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genetics
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genome-wide association study
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genotype environment interaction
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human
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metabolism
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phenotype
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physiology
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quantitative trait locus
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Alleles
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Binding Sites
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Gene Knockdown Techniques
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Gene-Environment Interaction
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Humans
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Interferon Regulatory Factor-1
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Models
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Genetic
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Quantitative Trait Loci
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Transcription Factors
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Tsu, A. L.
(författare)
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Kasela, S.
(författare)
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Kim-Hellmuth, S.
(författare)
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Aguet, F.
(författare)
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Ardlie, K. G.
(författare)
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Bussemaker, H. J.
(författare)
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Mohammadi, P.
(författare)
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Lappalainen, TuuliKTH,Genteknologi(Swepub:kth)u1o81n30
(författare)
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KTHGenteknologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:PLOS Genetics: Public Library of Science (PLoS)18:1, s. e1009719-1553-73901553-7404
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