Comparing autism phenotypes in children born extremely preterm and born at term / Robert M. JOSEPH in Autism Research, 16-3 (March 2023)  

Public ISBD [article]  inAutism Research > 16-3 (March 2023) . - p.653-666 Titre : Comparing autism phenotypes in children born extremely preterm and born at term Type de document : texte imprimé Auteurs : Robert M. JOSEPH, Auteur ; Emily R. LAI, Auteur ; Somer L. BISHOP, Auteur ; Joe YI, Auteur ; Margaret L. BAUMAN, Auteur ; Jean A. FRAZIER, Auteur ; Hudson P. Jr SANTOS, Auteur ; Laurie M. DOUGLAS, Auteur ; Karl C.K. KUBAN, Auteur ; Rebecca C. FRY, Auteur ; T. Michael O'SHEA, Auteur Article en page(s) : p.653-666 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Children born preterm are at increased risk for autism spectrum disorder (ASD). There is limited knowledge about whether ASD phenotypes in children born preterm differ from children born at term. The objective of this study was to compare ASD core symptoms and associated characteristics among extremely preterm (EP) and term-born children with ASD. EP participants (n = 59) from the Extremely Low Gestational Age Newborn Study who met diagnostic criteria for ASD at approximately 10 years of age were matched with term-born participants from the Simons Simplex Collection on age, sex, spoken language level, and nonverbal IQ. Core ASD symptomatology was evaluated with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Developmental milestones, anthropometrics, seizure disorder, and psychiatric symptoms were also investigated. The EP group had lower parent-reported symptom scores on ADI-R verbal communication, specifically stereotyped language, and restricted, repetitive behaviors. There were no between-group differences on ADI-R nonverbal communication and ADI-R reciprocal social interaction or with direct observation on the ADOS-2. The EP group was more likely to have delayed speech milestones and lower physical growth parameters. Results from female-only analyses were similar to those from whole-group analyses. In sum, behavioral presentation was similar between EP and IQ- and sex-matched term-born children assessed at age 10 years, with the exception of less severe retrospectively reported stereotyped behaviors, lower physical growth parameters, and increased delays in language milestones among EP-born children with ASD. En ligne : https://doi.org/10.1002/aur.2885 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=499 [article] Comparing autism phenotypes in children born extremely preterm and born at term [texte imprimé] / Robert M. JOSEPH, Auteur ; Emily R. LAI, Auteur ; Somer L. BISHOP, Auteur ; Joe YI, Auteur ; Margaret L. BAUMAN, Auteur ; Jean A. FRAZIER, Auteur ; Hudson P. Jr SANTOS, Auteur ; Laurie M. DOUGLAS, Auteur ; Karl C.K. KUBAN, Auteur ; Rebecca C. FRY, Auteur ; T. Michael O'SHEA, Auteur . - p.653-666. Langues : Anglais (eng) in Autism Research > 16-3 (March 2023) . - p.653-666 Index. décimale : PER Périodiques Résumé : Abstract Children born preterm are at increased risk for autism spectrum disorder (ASD). There is limited knowledge about whether ASD phenotypes in children born preterm differ from children born at term. The objective of this study was to compare ASD core symptoms and associated characteristics among extremely preterm (EP) and term-born children with ASD. EP participants (n = 59) from the Extremely Low Gestational Age Newborn Study who met diagnostic criteria for ASD at approximately 10 years of age were matched with term-born participants from the Simons Simplex Collection on age, sex, spoken language level, and nonverbal IQ. Core ASD symptomatology was evaluated with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Developmental milestones, anthropometrics, seizure disorder, and psychiatric symptoms were also investigated. The EP group had lower parent-reported symptom scores on ADI-R verbal communication, specifically stereotyped language, and restricted, repetitive behaviors. There were no between-group differences on ADI-R nonverbal communication and ADI-R reciprocal social interaction or with direct observation on the ADOS-2. The EP group was more likely to have delayed speech milestones and lower physical growth parameters. Results from female-only analyses were similar to those from whole-group analyses. In sum, behavioral presentation was similar between EP and IQ- and sex-matched term-born children assessed at age 10 years, with the exception of less severe retrospectively reported stereotyped behaviors, lower physical growth parameters, and increased delays in language milestones among EP-born children with ASD. En ligne : https://doi.org/10.1002/aur.2885 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=499

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)  

Public ISBD [article]  inMolecular Autism > 11 (2020) 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 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 [article] Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm [texte imprimé] / 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

Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm / Weifang LIU in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm Type de document : texte imprimé Auteurs : Weifang LIU, Auteur ; Quan SUN, Auteur ; Le HUANG, Auteur ; Arjun BHATTACHARYA, Auteur ; Geoffery W. WANG, Auteur ; Xianming TAN, Auteur ; Karl C.K. KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur ; Yun LI, Auteur ; Hudson P. Jr SANTOS, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Brain  Child  Child, Preschool  Cognitive Dysfunction/genetics  DNA-Binding Proteins  Genome-Wide Association Study  Humans  Infant, Extremely Premature/psychology  Infant, Newborn  Muscle Proteins  Prospective Studies  TEA Domain Transcription Factors  Transcription Factors  Young Adult  Cognitive impairment  Genetic mechanisms  Genome-wide association study (GWAS)  Latent profile analysis (LPA)  Neurodevelopment  Preterm children Index. décimale : PER Périodiques Résumé : BACKGROUND: Although survival rates for infants born extremely preterm (gestation < 28 weeks) have improved significantly in recent decades, neurodevelopmental impairment remains a major concern. Children born extremely preterm remain at high risk for cognitive impairment from early childhood to adulthood. However, there is limited evidence on genetic factors associated with cognitive impairment in this population. METHODS: First, we used a latent profile analysis (LPA) approach to characterize neurocognitive function at age 10 for children born extremely preterm. Children were classified into two groups: (1) no or low cognitive impairment, and (2) moderate-to-severe cognitive impairment. Second, we performed TOPMed-based genotype imputation on samples with genotype array data (n = 528). Third, we then conducted a genome-wide association study (GWAS) for LPA-inferred cognitive impairment. Finally, computational analysis was conducted to explore potential mechanisms underlying the variant x LPA association. RESULTS: We identified two loci reaching genome-wide significance (p value < 5e-8): TEA domain transcription factor 4 (TEAD4 at rs11829294, p value = 2.40e-8) and syntaxin 18 (STX18 at rs79453226, p value = 1.91e-8). Integrative analysis with brain expression quantitative trait loci (eQTL), chromatin conformation, and epigenomic annotations suggests tetraspanin 9 (TSPAN9) and protein arginine methyltransferase 8 (PRMT8) as potential functional genes underlying the GWAS signal at the TEAD4 locus. CONCLUSIONS: We conducted a novel computational analysis by utilizing an LPA-inferred phenotype with genetics data for the first time. This study suggests that rs11829294 and its LD buddies have potential regulatory roles on genes that could impact neurocognitive impairment for extreme preterm born children. En ligne : https://dx.doi.org/10.1186/s11689-022-09429-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm [texte imprimé] / Weifang LIU, Auteur ; Quan SUN, Auteur ; Le HUANG, Auteur ; Arjun BHATTACHARYA, Auteur ; Geoffery W. WANG, Auteur ; Xianming TAN, Auteur ; Karl C.K. KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur ; Yun LI, Auteur ; Hudson P. Jr SANTOS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Brain  Child  Child, Preschool  Cognitive Dysfunction/genetics  DNA-Binding Proteins  Genome-Wide Association Study  Humans  Infant, Extremely Premature/psychology  Infant, Newborn  Muscle Proteins  Prospective Studies  TEA Domain Transcription Factors  Transcription Factors  Young Adult  Cognitive impairment  Genetic mechanisms  Genome-wide association study (GWAS)  Latent profile analysis (LPA)  Neurodevelopment  Preterm children Index. décimale : PER Périodiques Résumé : BACKGROUND: Although survival rates for infants born extremely preterm (gestation < 28 weeks) have improved significantly in recent decades, neurodevelopmental impairment remains a major concern. Children born extremely preterm remain at high risk for cognitive impairment from early childhood to adulthood. However, there is limited evidence on genetic factors associated with cognitive impairment in this population. METHODS: First, we used a latent profile analysis (LPA) approach to characterize neurocognitive function at age 10 for children born extremely preterm. Children were classified into two groups: (1) no or low cognitive impairment, and (2) moderate-to-severe cognitive impairment. Second, we performed TOPMed-based genotype imputation on samples with genotype array data (n = 528). Third, we then conducted a genome-wide association study (GWAS) for LPA-inferred cognitive impairment. Finally, computational analysis was conducted to explore potential mechanisms underlying the variant x LPA association. RESULTS: We identified two loci reaching genome-wide significance (p value < 5e-8): TEA domain transcription factor 4 (TEAD4 at rs11829294, p value = 2.40e-8) and syntaxin 18 (STX18 at rs79453226, p value = 1.91e-8). Integrative analysis with brain expression quantitative trait loci (eQTL), chromatin conformation, and epigenomic annotations suggests tetraspanin 9 (TSPAN9) and protein arginine methyltransferase 8 (PRMT8) as potential functional genes underlying the GWAS signal at the TEAD4 locus. CONCLUSIONS: We conducted a novel computational analysis by utilizing an LPA-inferred phenotype with genetics data for the first time. This study suggests that rs11829294 and its LD buddies have potential regulatory roles on genes that could impact neurocognitive impairment for extreme preterm born children. En ligne : https://dx.doi.org/10.1186/s11689-022-09429-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

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)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 57-2 (February 2016) . - p.152-160 Titre : Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 Type de document : texte imprimé Auteurs : Beth WILMOT, Auteur ; Rebecca C. 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 [article] Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2 [texte imprimé] / Beth WILMOT, Auteur ; Rebecca C. 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

A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm / Anastasia N. FREEDMAN in Autism Research, 16-5 (May 2023)  

Public ISBD [article]  inAutism Research > 16-5 (May 2023) . - p.918-934 Titre : A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm Type de document : texte imprimé Auteurs : Anastasia N. FREEDMAN, Auteur ; Jeliyah CLARK, Auteur ; Lauren A. EAVES, Auteur ; Kyle ROELL, Auteur ; Ali ORAN, Auteur ; Lauren KOVAL, Auteur ; Julia RAGER, Auteur ; Hudson P. Jr SANTOS, Auteur ; Karl C.K. KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; Jean A. FRAZIER, Auteur ; Carmen J. MARSIT, Auteur ; Amber A. BURT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur Article en page(s) : p.918-934 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Abstract Children born preterm are at heightened risk of neurodevelopmental impairments, including Autism Spectrum Disorder (ASD). The placenta is a key regulator of neurodevelopmental processes, though the precise underlying molecular mechanisms remain unclear. Here, we employed a multi-omic approach to identify placental transcriptomic and epigenetic modifications related to ASD diagnosis at age 10, among children born preterm. Working with the extremely low gestational age (ELGAN) cohort, we hypothesized that a pro-inflammatory placental environment would be predictive of ASD diagnosis at age 10. Placental messenger RNA (mRNA) expression, CpG methylation, and microRNA (miRNA) expression were compared among 368 ELGANs (28 children diagnosed with ASD and 340 children without ASD). A total of 111 genes displayed expression levels in the placenta that were associated with ASD. Within these ASD-associated genes is an ASD regulatory complex comprising key genes that predicted ASD case status. Genes with expression that predicted ASD case status included Ewing Sarcoma Breakpoint Region 1 (EWSR1) (OR: 6.57 (95% CI: 2.34, 23.58)) and Bromodomain Adjacent To Zinc Finger Domain 2A (BAZ2A) (OR: 0.12 (95% CI: 0.03, 0.35)). Moreover, of the 111 ASD-associated genes, nine (8.1%) displayed associations with CpG methylation levels, while 14 (12.6%) displayed associations with miRNA expression levels. Among these, LRR Binding FLII Interacting Protein 1 (LRRFIP1) was identified as being under the control of both CpG methylation and miRNAs, displaying an OR of 0.42 (95% CI: 0.17, 0.95). This gene, as well as others identified as having functional epimutations, plays a critical role in immune system regulation and inflammatory response. In summary, a multi-omic approach was used to identify functional epimutations in the placenta that are associated with the development of ASD in children born preterm, highlighting future avenues for intervention. En ligne : http://dx.doi.org/https://doi.org/10.1002/aur.2915 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=503 [article] A multi-omic approach identifies an autism spectrum disorder (ASD) regulatory complex of functional epimutations in placentas from children born preterm [texte imprimé] / Anastasia N. FREEDMAN, Auteur ; Jeliyah CLARK, Auteur ; Lauren A. EAVES, Auteur ; Kyle ROELL, Auteur ; Ali ORAN, Auteur ; Lauren KOVAL, Auteur ; Julia RAGER, Auteur ; Hudson P. Jr SANTOS, Auteur ; Karl C.K. KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; Jean A. FRAZIER, Auteur ; Carmen J. MARSIT, Auteur ; Amber A. BURT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur . - p.918-934. Langues : Anglais (eng) in Autism Research > 16-5 (May 2023) . - p.918-934 Index. décimale : PER Périodiques Résumé : Abstract Children born preterm are at heightened risk of neurodevelopmental impairments, including Autism Spectrum Disorder (ASD). The placenta is a key regulator of neurodevelopmental processes, though the precise underlying molecular mechanisms remain unclear. Here, we employed a multi-omic approach to identify placental transcriptomic and epigenetic modifications related to ASD diagnosis at age 10, among children born preterm. Working with the extremely low gestational age (ELGAN) cohort, we hypothesized that a pro-inflammatory placental environment would be predictive of ASD diagnosis at age 10. Placental messenger RNA (mRNA) expression, CpG methylation, and microRNA (miRNA) expression were compared among 368 ELGANs (28 children diagnosed with ASD and 340 children without ASD). A total of 111 genes displayed expression levels in the placenta that were associated with ASD. Within these ASD-associated genes is an ASD regulatory complex comprising key genes that predicted ASD case status. Genes with expression that predicted ASD case status included Ewing Sarcoma Breakpoint Region 1 (EWSR1) (OR: 6.57 (95% CI: 2.34, 23.58)) and Bromodomain Adjacent To Zinc Finger Domain 2A (BAZ2A) (OR: 0.12 (95% CI: 0.03, 0.35)). Moreover, of the 111 ASD-associated genes, nine (8.1%) displayed associations with CpG methylation levels, while 14 (12.6%) displayed associations with miRNA expression levels. Among these, LRR Binding FLII Interacting Protein 1 (LRRFIP1) was identified as being under the control of both CpG methylation and miRNAs, displaying an OR of 0.42 (95% CI: 0.17, 0.95). This gene, as well as others identified as having functional epimutations, plays a critical role in immune system regulation and inflammatory response. In summary, a multi-omic approach was used to identify functional epimutations in the placenta that are associated with the development of ASD in children born preterm, highlighting future avenues for intervention. En ligne : http://dx.doi.org/https://doi.org/10.1002/aur.2915 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=503

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