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Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment
The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non‐typical development (Non‐TD) is poorly understood. Maternal blood collect...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894157/ https://www.ncbi.nlm.nih.gov/pubmed/33159718 http://dx.doi.org/10.1002/aur.2428 |
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author | Zhu, Yihui Mordaunt, Charles E. Durbin‐Johnson, Blythe P. Caudill, Marie A. Malysheva, Olga V. Miller, Joshua W. Green, Ralph James, S. Jill Melnyk, Stepan B. Fallin, M. Daniele Hertz‐Picciotto, Irva Schmidt, Rebecca J. LaSalle, Janine M. |
author_facet | Zhu, Yihui Mordaunt, Charles E. Durbin‐Johnson, Blythe P. Caudill, Marie A. Malysheva, Olga V. Miller, Joshua W. Green, Ralph James, S. Jill Melnyk, Stepan B. Fallin, M. Daniele Hertz‐Picciotto, Irva Schmidt, Rebecca J. LaSalle, Janine M. |
author_sort | Zhu, Yihui |
collection | PubMed |
description | The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non‐typical development (Non‐TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one‐carbon metabolites, on gene pathways and neurodevelopment. Genome‐wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies‐Learning Early Signs. Sixteen different one‐carbon metabolites, including folic acid, betaine, 5′‐methyltretrahydrofolate (5‐MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non‐TD and ASD, and to one‐carbon metabolites. Using differential gene expression analysis, six transcripts (TGR‐AS1, SQSTM1, HLA‐C, and RFESD) were associated with child outcomes (ASD, Non‐TD, and TD) with genome‐wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co‐expressed gene modules significantly correlated with 5‐MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5‐MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co‐expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one‐carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non‐typical neurodevelopment and were associated with maternal nutrients. |
format | Online Article Text |
id | pubmed-7894157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78941572021-03-02 Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment Zhu, Yihui Mordaunt, Charles E. Durbin‐Johnson, Blythe P. Caudill, Marie A. Malysheva, Olga V. Miller, Joshua W. Green, Ralph James, S. Jill Melnyk, Stepan B. Fallin, M. Daniele Hertz‐Picciotto, Irva Schmidt, Rebecca J. LaSalle, Janine M. Autism Res OMICS The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non‐typical development (Non‐TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one‐carbon metabolites, on gene pathways and neurodevelopment. Genome‐wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies‐Learning Early Signs. Sixteen different one‐carbon metabolites, including folic acid, betaine, 5′‐methyltretrahydrofolate (5‐MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non‐TD and ASD, and to one‐carbon metabolites. Using differential gene expression analysis, six transcripts (TGR‐AS1, SQSTM1, HLA‐C, and RFESD) were associated with child outcomes (ASD, Non‐TD, and TD) with genome‐wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co‐expressed gene modules significantly correlated with 5‐MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5‐MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co‐expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one‐carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non‐typical neurodevelopment and were associated with maternal nutrients. John Wiley & Sons, Inc. 2020-11-07 2021-01 /pmc/articles/PMC7894157/ /pubmed/33159718 http://dx.doi.org/10.1002/aur.2428 Text en © 2020 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | OMICS Zhu, Yihui Mordaunt, Charles E. Durbin‐Johnson, Blythe P. Caudill, Marie A. Malysheva, Olga V. Miller, Joshua W. Green, Ralph James, S. Jill Melnyk, Stepan B. Fallin, M. Daniele Hertz‐Picciotto, Irva Schmidt, Rebecca J. LaSalle, Janine M. Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment |
title | Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment |
title_full | Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment |
title_fullStr | Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment |
title_full_unstemmed | Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment |
title_short | Expression Changes in Epigenetic Gene Pathways Associated With One‐Carbon Nutritional Metabolites in Maternal Blood From Pregnancies Resulting in Autism and Non‐Typical Neurodevelopment |
title_sort | expression changes in epigenetic gene pathways associated with one‐carbon nutritional metabolites in maternal blood from pregnancies resulting in autism and non‐typical neurodevelopment |
topic | OMICS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894157/ https://www.ncbi.nlm.nih.gov/pubmed/33159718 http://dx.doi.org/10.1002/aur.2428 |
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