Placental genomics mediates genetic associations with complex health traits and disease Article Swipe
Arjun Bhattacharya
,
Anastasia N. Freedman
,
Vennela Avula
,
Rebeca Harris
,
Weifang Liu
,
Calvin Pan
,
Aldons J. Lusis
,
Robert Joseph
,
Lisa Smeester
,
Hadley J. Hartwell
,
Karl Kuban
,
Carmen J. Marsit
,
Yun Li
,
T. Michael O’Shea
,
Rebecca C. Fry
,
Hudson P. Santos
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-022-28365-x
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-022-28365-x
As the master regulator in utero , the placenta is core to the Developmental Origins of Health and Disease (DOHaD) hypothesis but is historically understudied. To identify placental gene-trait associations (GTAs) across the life course, we perform distal mediator-enriched transcriptome-wide association studies (TWAS) for 40 traits, integrating placental multi-omics from the Extremely Low Gestational Age Newborn Study. At $$P \; < \; 2.5\times {10}^{-6}$$ , we detect 248 GTAs, mostly for neonatal and metabolic traits, across 176 genes, enriched for cell growth and immunological pathways. In aggregate, genetic effects mediated by placental expression significantly explain 4 early-life traits but no later-in-life traits. 89 GTAs show significant mediation through distal genetic variants, identifying hypotheses for distal regulation of GTAs. Investigation of one hypothesis in human placenta-derived choriocarcinoma cells reveal that knockdown of mediator gene EPS15 upregulates predicted targets SPATA13 and FAM214A , both associated with waist-hip ratio in TWAS, and multiple genes involved in metabolic pathways. These results suggest profound health impacts of placental genomic regulation in developmental programming across the life course.
Related Topics
Concepts
Biology
Transcriptome
Genetics
Mediator
Gene
Placenta
Epigenetics
Epigenome
Gene knockdown
Disease
Genome-wide association study
Gene expression
DNA methylation
Pregnancy
Single-nucleotide polymorphism
Genotype
Endocrinology
Internal medicine
Medicine
Fetus
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41467-022-28365-x
- https://www.nature.com/articles/s41467-022-28365-x.pdf
- OA Status
- gold
- Cited By
- 44
- References
- 128
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4213179335
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4213179335Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41467-022-28365-xDigital Object Identifier
- Title
-
Placental genomics mediates genetic associations with complex health traits and diseaseWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-02-04Full publication date if available
- Authors
-
Arjun Bhattacharya, Anastasia N. Freedman, Vennela Avula, Rebeca Harris, Weifang Liu, Calvin Pan, Aldons J. Lusis, Robert Joseph, Lisa Smeester, Hadley J. Hartwell, Karl Kuban, Carmen J. Marsit, Yun Li, T. Michael O’Shea, Rebecca C. Fry, Hudson P. SantosList of authors in order
- Landing page
-
https://doi.org/10.1038/s41467-022-28365-xPublisher landing page
- PDF URL
-
https://www.nature.com/articles/s41467-022-28365-x.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.nature.com/articles/s41467-022-28365-x.pdfDirect OA link when available
- Concepts
-
Biology, Transcriptome, Genetics, Mediator, Gene, Placenta, Epigenetics, Epigenome, Gene knockdown, Disease, Genome-wide association study, Gene expression, DNA methylation, Pregnancy, Single-nucleotide polymorphism, Genotype, Endocrinology, Internal medicine, Medicine, FetusTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
44Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 12, 2024: 11, 2023: 10, 2022: 10, 2021: 1Per-year citation counts (last 5 years)
- References (count)
-
128Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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