Evidence map›Paper›PMID 39053458›Full record

ArticleAmerican journal of human genetics2024

Misexpression of inactive genes in whole blood is associated with nearby rare structural variants.

Thomas Vanderstichele, Katie L Burnham, Niek de Klein, Manuel Tardaguila, Brittany Howell, Klaudia Walter, Kousik Kundu, Jonas Koeppel, Wanseon Lee, Alex Tokolyi and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Thomas VandersticheleWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Katie L BurnhamWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Niek de KleinWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Manuel TardaguilaHuman Technopole, Fondazione Human Technopole, Milan, Italy.
Brittany HowellWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Klaudia WalterWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Kousik KunduWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Puddicombe Way, Cambridge, UK.
Jonas KoeppelWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Wanseon LeeWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Alex TokolyiWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Elodie PersynBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Artika P NathCambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Jonathan MartenBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Slavé PetrovskiCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; Department of Medicine, University of Melbourne, Austin Health, Melbourne, VIC, Australia.
David J RobertsRadcliffe Department of Medicine, John Radcliffe Hospital, Oxford, UK; Clinical Services, NHS Blood and Transplant, Oxford Centre, John Radcliffe Hospital, Oxford, UK.
Emanuele Di AngelantonioHuman Technopole, Fondazione Human Technopole, Milan, Italy; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
John DaneshWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Alix BertonTranslational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Molndal, Sweden.
Adam PlattTranslational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Adam S ButterworthBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Nicole SoranzoWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK; Human Technopole, Fondazione Human Technopole, Milan, Italy; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Puddicombe Way, Cambridge, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
Leopold PartsWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Michael InouyeBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Dirk S PaulBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Emma E DavenportWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. Electronic address: ed5@sanger.ac.uk.

Funding

Wellcome TrustWellcome Trust 206194Wellcome Trust 220540/Z/20/AWellcome Trust WT223718/Z/21/Z
6 · The paper itself

Abstract

Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors. We found that while individual misexpression events occur rarely, in aggregate they were found in almost all samples and a third of inactive protein-coding genes. Using 2,821 paired whole-genome and RNA sequencing samples, we identified that misexpression events are enriched in cis for rare structural variants. We established putative mechanisms through which a subset of SVs lead to gene misexpression, including transcriptional readthrough, transcript fusions, and gene inversion. Overall, we develop misexpression as a type of transcriptomic outlier analysis and extend our understanding of the variety of mechanisms by which genetic variants can influence gene expression.

Indexed as

Gene Expression RegulationBlood DonorsGenetic VariationGenomic Structural VariationHumansSequence Analysis, RNATranscriptomeaberrant expressionectopic expressionmisexpressionstructural variantstranscript fusiontranscriptional readthroughtranscriptomic outlier

Identifiers

PMID39053458
PMCPMC11339615

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.