Disease-associated variants are enriched for altering cell-type-specific gene co-expression relationships Article Swipe
Dan Kaptijn
,
Corinna Losert
,
Maryna Korshevniuk
,
Roy Oelen
,
Martijn Vochteloo
,
Patrick Deelen
,
Robert Warmerdam
,
Anoek Kooijmans
,
Daniel Considine
,
Yakov A. Tsepilov
,
Harm-Jan Westra
,
Monique G.P. van der Wijst
,
Marc Jan Bonder
,
Matthias Heinig
,
Lude Franke
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.09.06.674678
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.09.06.674678
Genes act within complex regulatory networks, and genetic variants can perturb these networks by altering gene co-expression. Here, we performed co-expression quantitative trait locus (co-eQTL) mapping using single-cell RNA-seq from the sc-eQTLGen consortium (1,330 donors, >2 million cells), enabling sensitive detection and prioritization of informative variant–gene–gene triplets. We identified co-eQTLs for 398 eGenes where a nearby genetic variant affected both the gene’s expression ( cis -gene) and its co-expression with other genes, often implicating upstream regulators. For 181 genes, we inferred a likely upstream transcription factor, with motif disruption predicted for 41 genes. These upstream genes are more often loss-of-function intolerant and show more network connections, providing an explanation for why co-eQTL variants are 2.8x more strongly associated with immune diseases than classical eQTLs. These findings position co-eQTLs as mechanistic links between genetic variation and disease, revealing how variants can rewire cell-type-specific gene networks.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.09.06.674678
- https://www.biorxiv.org/content/biorxiv/early/2025/09/08/2025.09.06.674678.full.pdf
- OA Status
- green
- References
- 60
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4414066273
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Raw OpenAlex JSON
- OpenAlex ID
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- DOI
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https://doi.org/10.1101/2025.09.06.674678Digital Object Identifier
- Title
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Disease-associated variants are enriched for altering cell-type-specific gene co-expression relationshipsWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-09-08Full publication date if available
- Authors
-
Dan Kaptijn, Corinna Losert, Maryna Korshevniuk, Roy Oelen, Martijn Vochteloo, Patrick Deelen, Robert Warmerdam, Anoek Kooijmans, Daniel Considine, Yakov A. Tsepilov, Harm-Jan Westra, Monique G.P. van der Wijst, Marc Jan Bonder, Matthias Heinig, Lude FrankeList of authors in order
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https://doi.org/10.1101/2025.09.06.674678Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2025/09/08/2025.09.06.674678.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/09/08/2025.09.06.674678.full.pdfDirect OA link when available
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.an | 108 |
| abstract_inverted_index.as | 129 |
| abstract_inverted_index.by | 14 |
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| abstract_inverted_index.we | 19, 80 |
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| abstract_inverted_index.398 | 52 |
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| abstract_inverted_index.and | 7, 42, 67, 102, 135 |
| abstract_inverted_index.are | 97, 114 |
| abstract_inverted_index.can | 10, 140 |
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| abstract_inverted_index.for | 51, 91, 110 |
| abstract_inverted_index.how | 138 |
| abstract_inverted_index.its | 68 |
| abstract_inverted_index.the | 31, 61 |
| abstract_inverted_index.why | 111 |
| abstract_inverted_index.2.8x | 115 |
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| abstract_inverted_index.from | 30 |
| abstract_inverted_index.gene | 16, 143 |
| abstract_inverted_index.more | 98, 104, 116 |
| abstract_inverted_index.show | 103 |
| abstract_inverted_index.than | 122 |
| abstract_inverted_index.with | 70, 87, 119 |
| abstract_inverted_index.>2 | 36 |
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| abstract_inverted_index.Here, | 18 |
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