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Auteur Lisa SMEESTER |
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Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm / Hudson P. Jr SANTOS in Molecular Autism, 11 (2020)
[article]
Titre : Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm Type de document : Texte imprimé et/ou numérique Auteurs : Hudson P. Jr SANTOS, Auteur ; Arjun BHATTACHARYA, Auteur ; Robert M. JOSEPH, Auteur ; Lisa SMEESTER, Auteur ; Karl C. K. KUBAN, Auteur ; Carmen J. MARSIT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur Langues : Anglais (eng) Mots-clés : Differential expression analysis Epigenome-wide association Multi-omic aggregation Placental gene regulation Prenatal neurodevelopmental programming Social and cognitive impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Children born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes. METHODS: We examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS. RESULTS: Genes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status. LIMITATIONS: The ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited. CONCLUSIONS: Aggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic. En ligne : http://dx.doi.org/10.1186/s13229-020-00402-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438
in Molecular Autism > 11 (2020)[article] Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm [Texte imprimé et/ou numérique] / Hudson P. Jr SANTOS, Auteur ; Arjun BHATTACHARYA, Auteur ; Robert M. JOSEPH, Auteur ; Lisa SMEESTER, Auteur ; Karl C. K. KUBAN, Auteur ; Carmen J. MARSIT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020)
Mots-clés : Differential expression analysis Epigenome-wide association Multi-omic aggregation Placental gene regulation Prenatal neurodevelopmental programming Social and cognitive impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Children born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes. METHODS: We examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS. RESULTS: Genes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status. LIMITATIONS: The ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited. CONCLUSIONS: Aggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic. En ligne : http://dx.doi.org/10.1186/s13229-020-00402-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 / Beth WILMOT in Journal of Child Psychology and Psychiatry, 57-2 (February 2016)
[article]
Titre : Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 Type de document : Texte imprimé et/ou numérique Auteurs : Beth WILMOT, Auteur ; Rebecca FRY, Auteur ; Lisa SMEESTER, Auteur ; Erica D. MUSSER, Auteur ; Jonathan MILL, Auteur ; Joel T. NIGG, Auteur Article en page(s) : p.152-160 Langues : Anglais (eng) Mots-clés : ADHD methylation epigenetic Index. décimale : PER Périodiques Résumé : Background Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene–environment interactions. We conducted an initial examination of CpG methylation variation in children with or without attention-deficit/hyperactivity disorder (ADHD). Methods Children age 7–12 were recruited, screened, evaluated and assigned to ADHD or non-ADHD groups by defined research criteria. Two independent age-matched samples were examined, a discovery set (n = 92, all boys, half control, half ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5-methylcytosine levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation array. Genes for which multiple probes were nominally significant and had a beta difference of at least 2% were evaluated for biological relevance and prioritized for confirmation and sequence validation. Gene pathways were explored and described. Results Two genes met the criteria for confirmation testing, VIPR2 and MYT1L; both had multiple probes meeting cutoffs and strong biological relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were confirmed through bisulfite sequencing. Enrichment analysis suggested involvement of gene sets or pathways related to inflammatory processes and modulation of monoamine and cholinergic neurotransmission. Conclusions Although it is unknown to what extent CpG methylation seen in peripheral tissue reflect transcriptomic changes in the brain, these initial results indicate that peripheral DNA methylation markers in ADHD may be promising and suggest targeted hypotheses for future study in larger samples. En ligne : http://dx.doi.org/10.1111/jcpp.12457 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280
in Journal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.152-160[article] Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 [Texte imprimé et/ou numérique] / Beth WILMOT, Auteur ; Rebecca FRY, Auteur ; Lisa SMEESTER, Auteur ; Erica D. MUSSER, Auteur ; Jonathan MILL, Auteur ; Joel T. NIGG, Auteur . - p.152-160.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.152-160
Mots-clés : ADHD methylation epigenetic Index. décimale : PER Périodiques Résumé : Background Peripheral epigenetic marks hold promise for understanding psychiatric illness and may represent fingerprints of gene–environment interactions. We conducted an initial examination of CpG methylation variation in children with or without attention-deficit/hyperactivity disorder (ADHD). Methods Children age 7–12 were recruited, screened, evaluated and assigned to ADHD or non-ADHD groups by defined research criteria. Two independent age-matched samples were examined, a discovery set (n = 92, all boys, half control, half ADHD) and a confirmation set (n = 20, half ADHD, all boys). 5-methylcytosine levels were quantified in salivary DNA using the Illumina 450 K HumanMethylation array. Genes for which multiple probes were nominally significant and had a beta difference of at least 2% were evaluated for biological relevance and prioritized for confirmation and sequence validation. Gene pathways were explored and described. Results Two genes met the criteria for confirmation testing, VIPR2 and MYT1L; both had multiple probes meeting cutoffs and strong biological relevance. Probes on VIPR2 passed FDR correction in the confirmation set and were confirmed through bisulfite sequencing. Enrichment analysis suggested involvement of gene sets or pathways related to inflammatory processes and modulation of monoamine and cholinergic neurotransmission. Conclusions Although it is unknown to what extent CpG methylation seen in peripheral tissue reflect transcriptomic changes in the brain, these initial results indicate that peripheral DNA methylation markers in ADHD may be promising and suggest targeted hypotheses for future study in larger samples. En ligne : http://dx.doi.org/10.1111/jcpp.12457 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=280