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Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

BACKGROUND: Accumulating evidence links paternal adiposity in the periconceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. METHODS: In the Pregnancy And Childhood Epigenetics (PACE...

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Autores principales: Sharp, Gemma C, Alfano, Rossella, Ghantous, Akram, Urquiza, Jose, Rifas-Shiman, Sheryl L, Page, Christian M, Jin, Jianping, Fernández-Barrés, Silvia, Santorelli, Gillian, Tindula, Gwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407864/
https://www.ncbi.nlm.nih.gov/pubmed/33517419
http://dx.doi.org/10.1093/ije/dyaa267
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author Sharp, Gemma C
Alfano, Rossella
Ghantous, Akram
Urquiza, Jose
Rifas-Shiman, Sheryl L
Page, Christian M
Jin, Jianping
Fernández-Barrés, Silvia
Santorelli, Gillian
Tindula, Gwen
author_facet Sharp, Gemma C
Alfano, Rossella
Ghantous, Akram
Urquiza, Jose
Rifas-Shiman, Sheryl L
Page, Christian M
Jin, Jianping
Fernández-Barrés, Silvia
Santorelli, Gillian
Tindula, Gwen
author_sort Sharp, Gemma C
collection PubMed
description BACKGROUND: Accumulating evidence links paternal adiposity in the periconceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. METHODS: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of coordinated epigenome-wide association studies (EWAS) of paternal prenatal body mass index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 data sets; total n = 4894) and in childhood (6 data sets; total n = 1982). RESULTS: We found little evidence of an association at either time point: at all CpGs, the false-discovery-rate-adjusted P-values were >0.05. In secondary sex-stratified analyses, we found just four CpGs for which there was robust evidence of an association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes. CONCLUSION: Our findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring-blood DNA methylation, even at imprinted regions.
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spelling pubmed-84078642021-09-01 Paternal body mass index and offspring DNA methylation: findings from the PACE consortium Sharp, Gemma C Alfano, Rossella Ghantous, Akram Urquiza, Jose Rifas-Shiman, Sheryl L Page, Christian M Jin, Jianping Fernández-Barrés, Silvia Santorelli, Gillian Tindula, Gwen Int J Epidemiol Genetics BACKGROUND: Accumulating evidence links paternal adiposity in the periconceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. METHODS: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of coordinated epigenome-wide association studies (EWAS) of paternal prenatal body mass index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 data sets; total n = 4894) and in childhood (6 data sets; total n = 1982). RESULTS: We found little evidence of an association at either time point: at all CpGs, the false-discovery-rate-adjusted P-values were >0.05. In secondary sex-stratified analyses, we found just four CpGs for which there was robust evidence of an association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes. CONCLUSION: Our findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring-blood DNA methylation, even at imprinted regions. Oxford University Press 2021-01-29 /pmc/articles/PMC8407864/ /pubmed/33517419 http://dx.doi.org/10.1093/ije/dyaa267 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genetics
Sharp, Gemma C
Alfano, Rossella
Ghantous, Akram
Urquiza, Jose
Rifas-Shiman, Sheryl L
Page, Christian M
Jin, Jianping
Fernández-Barrés, Silvia
Santorelli, Gillian
Tindula, Gwen
Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
title Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
title_full Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
title_fullStr Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
title_full_unstemmed Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
title_short Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
title_sort paternal body mass index and offspring dna methylation: findings from the pace consortium
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407864/
https://www.ncbi.nlm.nih.gov/pubmed/33517419
http://dx.doi.org/10.1093/ije/dyaa267
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