Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation

Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci.Ob...

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Autores principales:	Kelly M. Bakulski, John F. Dou, Jason I. Feinberg, Max T. Aung, Christine Ladd-Acosta, Heather E. Volk, Craig J. Newschaffer, Lisa A. Croen, Irva Hertz-Picciotto, Susan E. Levy, Rebecca Landa, Andrew P. Feinberg, Margaret D. Fallin
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	autism spectrum disorder DNA methylation biomarker epidemiology cord blood Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5b9805a95b324bdf95df54764765e973
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spelling	oai:doaj.org-article:5b9805a95b324bdf95df54764765e9732021-12-01T01:08:32ZAutism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation1662-509910.3389/fnmol.2021.775390https://doaj.org/article/5b9805a95b324bdf95df54764765e9732021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.775390/fullhttps://doaj.org/toc/1662-5099Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci.Objectives: To estimate associations between DNA methylation in maternal blood, cord blood, and placenta and later diagnosis of ASD, and to evaluate enrichment of ASD-associated DNA methylation for known ASD-associated genes.Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched risk birth cohort, genome-scale maternal blood (early n = 140 and late n = 75 pregnancy), infant cord blood (n = 133), and placenta (maternal n = 106 and fetal n = 107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. Differences in site-specific and global methylation were tested with ASD, as well as enrichment of single site associations for ASD risk genes (n = 881) from the Simons Foundation Autism Research Initiative (SFARI) database.Results: No individual DNA methylation site was associated with ASD at genome-wide significance, however, individual DNA methylation sites nominally associated with ASD (P < 0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 7.9 × 10–29, maternal blood early pregnancy P = 6.1 × 10–27, maternal blood late pregnancy P = 2.8 × 10–16, maternal placenta P = 5.6 × 10–15, fetal placenta P = 1.3 × 10–20). DNA methylation sites nominally associated with ASD across all five tissues overlapped at 144 (29.5%) SFARI genes.Conclusion: DNA methylation sites nominally associated with later ASD diagnosis in multiple tissues were enriched for ASD risk genes. Our multi-tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis.Kelly M. BakulskiJohn F. DouJason I. FeinbergJason I. FeinbergJason I. FeinbergMax T. AungChristine Ladd-AcostaChristine Ladd-AcostaHeather E. VolkHeather E. VolkCraig J. NewschafferLisa A. CroenIrva Hertz-PicciottoIrva Hertz-PicciottoSusan E. LevyRebecca LandaAndrew P. FeinbergAndrew P. FeinbergAndrew P. FeinbergMargaret D. FallinMargaret D. FallinMargaret D. FallinFrontiers Media S.A.articleautism spectrum disorderDNA methylationbiomarkerepidemiologycord bloodNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autism spectrum disorder DNA methylation biomarker epidemiology cord blood Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	autism spectrum disorder DNA methylation biomarker epidemiology cord blood Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Kelly M. Bakulski John F. Dou Jason I. Feinberg Jason I. Feinberg Jason I. Feinberg Max T. Aung Christine Ladd-Acosta Christine Ladd-Acosta Heather E. Volk Heather E. Volk Craig J. Newschaffer Lisa A. Croen Irva Hertz-Picciotto Irva Hertz-Picciotto Susan E. Levy Rebecca Landa Andrew P. Feinberg Andrew P. Feinberg Andrew P. Feinberg Margaret D. Fallin Margaret D. Fallin Margaret D. Fallin Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
description	Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci.Objectives: To estimate associations between DNA methylation in maternal blood, cord blood, and placenta and later diagnosis of ASD, and to evaluate enrichment of ASD-associated DNA methylation for known ASD-associated genes.Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched risk birth cohort, genome-scale maternal blood (early n = 140 and late n = 75 pregnancy), infant cord blood (n = 133), and placenta (maternal n = 106 and fetal n = 107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. Differences in site-specific and global methylation were tested with ASD, as well as enrichment of single site associations for ASD risk genes (n = 881) from the Simons Foundation Autism Research Initiative (SFARI) database.Results: No individual DNA methylation site was associated with ASD at genome-wide significance, however, individual DNA methylation sites nominally associated with ASD (P < 0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 7.9 × 10–29, maternal blood early pregnancy P = 6.1 × 10–27, maternal blood late pregnancy P = 2.8 × 10–16, maternal placenta P = 5.6 × 10–15, fetal placenta P = 1.3 × 10–20). DNA methylation sites nominally associated with ASD across all five tissues overlapped at 144 (29.5%) SFARI genes.Conclusion: DNA methylation sites nominally associated with later ASD diagnosis in multiple tissues were enriched for ASD risk genes. Our multi-tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis.
format	article
author	Kelly M. Bakulski John F. Dou Jason I. Feinberg Jason I. Feinberg Jason I. Feinberg Max T. Aung Christine Ladd-Acosta Christine Ladd-Acosta Heather E. Volk Heather E. Volk Craig J. Newschaffer Lisa A. Croen Irva Hertz-Picciotto Irva Hertz-Picciotto Susan E. Levy Rebecca Landa Andrew P. Feinberg Andrew P. Feinberg Andrew P. Feinberg Margaret D. Fallin Margaret D. Fallin Margaret D. Fallin
author_facet	Kelly M. Bakulski John F. Dou Jason I. Feinberg Jason I. Feinberg Jason I. Feinberg Max T. Aung Christine Ladd-Acosta Christine Ladd-Acosta Heather E. Volk Heather E. Volk Craig J. Newschaffer Lisa A. Croen Irva Hertz-Picciotto Irva Hertz-Picciotto Susan E. Levy Rebecca Landa Andrew P. Feinberg Andrew P. Feinberg Andrew P. Feinberg Margaret D. Fallin Margaret D. Fallin Margaret D. Fallin
author_sort	Kelly M. Bakulski
title	Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
title_short	Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
title_full	Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
title_fullStr	Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
title_full_unstemmed	Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation
title_sort	autism-associated dna methylation at birth from multiple tissues is enriched for autism genes in the early autism risk longitudinal investigation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5b9805a95b324bdf95df54764765e973
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Autism-Associated DNA Methylation at Birth From Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation

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