Genetically-predicted placental gene expression is associated with birthweight and adult body mass index

Elizabeth A. Jasper, Jacklyn N. Hellwege, Jacqueline A. Piekos, Sarah H. Jones, Katherine E. Hartmann, Brian Mautz, David M. Aronoff, Todd L. Edwards, Digna R.Velez Edwards

Research output: Contribution to journalArticlepeer-review

Abstract

The placenta is critical to human growth and development and has been implicated in health outcomes. Understanding the mechanisms through which the placenta influences perinatal and later-life outcomes requires further investigation. We evaluated the relationships between birthweight and adult body mass index (BMI) and genetically-predicted gene expression in human placenta. Birthweight genome-wide association summary statistics were obtained from the Early Growth Genetics Consortium (N = 298,142). Adult BMI summary statistics were obtained from the GIANT consortium (N = 681,275). We used S-PrediXcan to evaluate associations between the outcomes and predicted gene expression in placental tissue and, to identify genes where placental expression was exclusively associated with the outcomes, compared to 48 other tissues (GTEx v7). We identified 24 genes where predicted placental expression was significantly associated with birthweight, 15 of which were not associated with birthweight in any other tissue. One of these genes has been previously linked to birthweight. Analyses identified 182 genes where placental expression was associated with adult BMI, 110 were not associated with BMI in any other tissue. Eleven genes that had placental gene expression levels exclusively associated with BMI have been previously associated with BMI. Expression of a single gene, PAX4, was associated with both outcomes exclusively in the placenta. Inter-individual variation of gene expression in placental tissue may contribute to observed variation in birthweight and adult BMI, supporting developmental origins hypothesis.

Original languageEnglish
Article number322
JournalScientific Reports
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

ASJC Scopus subject areas

  • General

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