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Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome
BACKGROUND: Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340003/ https://www.ncbi.nlm.nih.gov/pubmed/28264723 http://dx.doi.org/10.1186/s12916-017-0800-1 |
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author | Lin, Xinyi Lim, Ives Yubin Wu, Yonghui Teh, Ai Ling Chen, Li Aris, Izzuddin M. Soh, Shu E. Tint, Mya Thway MacIsaac, Julia L. Morin, Alexander M. Yap, Fabian Tan, Kok Hian Saw, Seang Mei Kobor, Michael S. Meaney, Michael J. Godfrey, Keith M. Chong, Yap Seng Holbrook, Joanna D. Lee, Yung Seng Gluckman, Peter D. Karnani, Neerja |
author_facet | Lin, Xinyi Lim, Ives Yubin Wu, Yonghui Teh, Ai Ling Chen, Li Aris, Izzuddin M. Soh, Shu E. Tint, Mya Thway MacIsaac, Julia L. Morin, Alexander M. Yap, Fabian Tan, Kok Hian Saw, Seang Mei Kobor, Michael S. Meaney, Michael J. Godfrey, Keith M. Chong, Yap Seng Holbrook, Joanna D. Lee, Yung Seng Gluckman, Peter D. Karnani, Neerja |
author_sort | Lin, Xinyi |
collection | PubMed |
description | BACKGROUND: Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood. In this study, we shed more light on this aspect by performing a comprehensive analysis on the effects of variation in prenatal environment, neonatal methylome, and genotype on birth weight and adiposity in early childhood. METHODS: In a prospective mother-offspring cohort (N = 987), we interrogated the effects of 30 variables that influence the prenatal environment, umbilical cord DNA methylation, and genotype on offspring weight and adiposity, over the period from birth to 48 months. This is an interim analysis on an ongoing cohort study. RESULTS: Eleven of 30 prenatal environments, including maternal adiposity, smoking, blood glucose and plasma unsaturated fatty acid levels, were associated with birth weight. Polygenic risk scores derived from genetic association studies on adult adiposity were also associated with birth weight and child adiposity, indicating an overlap between the genetic pathways influencing metabolic health in early and later life. Neonatal methylation markers from seven gene loci (ANK3, CDKN2B, CACNA1G, IGDCC4, P4HA3, ZNF423 and MIRLET7BHG) were significantly associated with birth weight, with a subset of these in genes previously implicated in metabolic pathways in humans and in animal models. Methylation levels at three of seven birth weight-linked loci showed significant association with prenatal environment, but none were affected by polygenic risk score. Six of these birth weight-linked loci continued to show a longitudinal association with offspring size and/or adiposity in early childhood. CONCLUSIONS: This study provides further evidence that developmental pathways to adiposity begin before birth and are influenced by environmental, genetic and epigenetic factors. These pathways can have a lasting effect on offspring size, adiposity and future metabolic outcomes, and offer new opportunities for risk stratification and prevention of obesity. CLINICAL TRIAL REGISTRATION: This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-017-0800-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5340003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53400032017-03-10 Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome Lin, Xinyi Lim, Ives Yubin Wu, Yonghui Teh, Ai Ling Chen, Li Aris, Izzuddin M. Soh, Shu E. Tint, Mya Thway MacIsaac, Julia L. Morin, Alexander M. Yap, Fabian Tan, Kok Hian Saw, Seang Mei Kobor, Michael S. Meaney, Michael J. Godfrey, Keith M. Chong, Yap Seng Holbrook, Joanna D. Lee, Yung Seng Gluckman, Peter D. Karnani, Neerja BMC Med Research Article BACKGROUND: Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood. In this study, we shed more light on this aspect by performing a comprehensive analysis on the effects of variation in prenatal environment, neonatal methylome, and genotype on birth weight and adiposity in early childhood. METHODS: In a prospective mother-offspring cohort (N = 987), we interrogated the effects of 30 variables that influence the prenatal environment, umbilical cord DNA methylation, and genotype on offspring weight and adiposity, over the period from birth to 48 months. This is an interim analysis on an ongoing cohort study. RESULTS: Eleven of 30 prenatal environments, including maternal adiposity, smoking, blood glucose and plasma unsaturated fatty acid levels, were associated with birth weight. Polygenic risk scores derived from genetic association studies on adult adiposity were also associated with birth weight and child adiposity, indicating an overlap between the genetic pathways influencing metabolic health in early and later life. Neonatal methylation markers from seven gene loci (ANK3, CDKN2B, CACNA1G, IGDCC4, P4HA3, ZNF423 and MIRLET7BHG) were significantly associated with birth weight, with a subset of these in genes previously implicated in metabolic pathways in humans and in animal models. Methylation levels at three of seven birth weight-linked loci showed significant association with prenatal environment, but none were affected by polygenic risk score. Six of these birth weight-linked loci continued to show a longitudinal association with offspring size and/or adiposity in early childhood. CONCLUSIONS: This study provides further evidence that developmental pathways to adiposity begin before birth and are influenced by environmental, genetic and epigenetic factors. These pathways can have a lasting effect on offspring size, adiposity and future metabolic outcomes, and offer new opportunities for risk stratification and prevention of obesity. CLINICAL TRIAL REGISTRATION: This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-017-0800-1) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-07 /pmc/articles/PMC5340003/ /pubmed/28264723 http://dx.doi.org/10.1186/s12916-017-0800-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Lin, Xinyi Lim, Ives Yubin Wu, Yonghui Teh, Ai Ling Chen, Li Aris, Izzuddin M. Soh, Shu E. Tint, Mya Thway MacIsaac, Julia L. Morin, Alexander M. Yap, Fabian Tan, Kok Hian Saw, Seang Mei Kobor, Michael S. Meaney, Michael J. Godfrey, Keith M. Chong, Yap Seng Holbrook, Joanna D. Lee, Yung Seng Gluckman, Peter D. Karnani, Neerja Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
title | Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
title_full | Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
title_fullStr | Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
title_full_unstemmed | Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
title_short | Developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
title_sort | developmental pathways to adiposity begin before birth and are influenced by genotype, prenatal environment and epigenome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340003/ https://www.ncbi.nlm.nih.gov/pubmed/28264723 http://dx.doi.org/10.1186/s12916-017-0800-1 |
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