Identifying links between cardiovascular disease and insomnia by modeling genes from a pleiotropic locus Article Swipe
Farah Abou Daya
,
Torrey Mandigo
,
Lily Ober
,
Dev Patel
,
Matthew Maher
,
Suresh Bada Math
,
Cynthia Tchio
,
James A. Walker
,
Richa Saxena
,
Girish C. Melkani
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1242/dmm.052139
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1242/dmm.052139
Insomnia symptoms double the risk of cardiovascular disease (CVD), yet shared genetic pathways remain unclear. Genome-wide association studies identified a genetic locus (near ATP5G1, UBE2Z, SNF8, IGF2BP1 and GIP) linked to insomnia and CVD. We used Drosophila models to perform tissue-specific RNA interference knockdowns of four conserved orthologs (ATPsynC, lsn, Bruce and Imp) in neurons and the heart. Neuronal-specific knockdown of ATPsynC, Imp and lsn impaired sleep quantity and quality. In contrast, cardiac knockdown of ATPsynC and lsn reduced cardiac function and lifespan, with lsn knockdown also causing cardiac dilation and myofibrillar disorganization. Cross-tissue effects were evident: neuronal Imp knockdown compromised cardiac function, whereas cardiac ATPsynC and lsn knockdown increased sleep fragmentation and inflammation (marked by Upd3 elevation in the heart or head). Overexpression of Upd3 in neurons impaired cardiac function, and its overexpression in the heart disrupted sleep. Our findings reveal conserved genes mediating tissue-specific and cross-tissue interactions between sleep and cardiac function, providing novel insights into the genetic mechanisms linking insomnia and CVD through inflammation.
Related Topics
Concepts
Gene knockdown
Biology
Genome-wide association study
Locus (genetics)
Genetics
RNA interference
Gene
Single-nucleotide polymorphism
Genotype
RNA
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1242/dmm.052139
- https://journals.biologists.com/dmm/article-pdf/doi/10.1242/dmm.052139/3642892/dmm052139.pdf
- OA Status
- gold
- Cited By
- 7
- References
- 72
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409115620
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409115620Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1242/dmm.052139Digital Object Identifier
- Title
-
Identifying links between cardiovascular disease and insomnia by modeling genes from a pleiotropic locusWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-04-03Full publication date if available
- Authors
-
Farah Abou Daya, Torrey Mandigo, Lily Ober, Dev Patel, Matthew Maher, Suresh Bada Math, Cynthia Tchio, James A. Walker, Richa Saxena, Girish C. MelkaniList of authors in order
- Landing page
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https://doi.org/10.1242/dmm.052139Publisher landing page
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https://journals.biologists.com/dmm/article-pdf/doi/10.1242/dmm.052139/3642892/dmm052139.pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://journals.biologists.com/dmm/article-pdf/doi/10.1242/dmm.052139/3642892/dmm052139.pdfDirect OA link when available
- Concepts
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Gene knockdown, Biology, Genome-wide association study, Locus (genetics), Genetics, RNA interference, Gene, Single-nucleotide polymorphism, Genotype, RNATop concepts (fields/topics) attached by OpenAlex
- Cited by
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7Total citation count in OpenAlex
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2025: 7Per-year citation counts (last 5 years)
- References (count)
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72Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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