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

doi:10.1038/s41598-022-26572-6

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 journal › Article › peer-review

4 Scopus citations

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 language	English
Article number	322
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-26572-6
State	Published - Dec 2023

Bibliographical note

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

Funding

The authors have no relevant financial or non-financial interests to disclose. Support for this research was provided by a National Institute on Minority Health and Health Disparities award for the Center of Excellence in Precision Medicine and Population Health (U54MD010722 to D.R.V.E.), a National Human Genome Research Institute award for the Vanderbilt Genomic Medicine Training Program (T32HG008341 to E.A.J.), a Eunice Kennedy Shriver National Institute of Child and Human Development award for the Building Interdisciplinary Research Careers in Women’s Health career development program (K12HD043483 to E.A.J. and J.N.H.), and a National Institute of General Medical Sciences award for the Training Program in Genetic Variation and Human Phenotypes (T32GM080178 to J.A.P.) at Vanderbilt University Medical Center.

Funders	Funder number
Eunice Kennedy Shriver National Institute of Child and Human Development award for the Building Interdisciplinary Research Careers in Women’s Health career development program
National Human Genome Research Institute	T32HG008341
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	T32GM080178
National Institute on Minority Health and Health Disparities (NIMHD)	U54MD010722
Eunice Kennedy Shriver National Institute of Child Health and Human Development	K12HD043483
Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General

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10.1038/s41598-022-26572-6

Cite this

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title = "Genetically-predicted placental gene expression is associated with birthweight and adult body mass index",

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.",

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doi = "10.1038/s41598-022-26572-6",

language = "English",

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AU - Jones, Sarah H.

AU - Hartmann, Katherine E.

AU - Mautz, Brian

AU - Aronoff, David M.

AU - Edwards, Todd L.

AU - Edwards, Digna R.Velez

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AB - 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.

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

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

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