Case-control meta-analysis of blood DNA methylation and autism spectrum disorder / S. V. ANDREWS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 40p. Titre : Case-control meta-analysis of blood DNA methylation and autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : S. V. ANDREWS, Auteur ; B. SHEPPARD, Auteur ; G. C. WINDHAM, Auteur ; Laura A. SCHIEVE, Auteur ; Diana SCHENDEL, Auteur ; Lisa A. CROEN, Auteur ; P. CHOPRA, Auteur ; R. S. ALISCH, Auteur ; C. J. NEWSCHAFFER, Auteur ; S. T. WARREN, Auteur ; A. P. FEINBERG, Auteur ; M. D. FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur Article en page(s) : 40p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/blood/genetics  Case-Control Studies  Child, Preschool  CpG Islands  DNA Methylation  Epigenesis, Genetic  Female  Genome-Wide Association Study  Humans  Male  Autism spectrum disorders  Epigenome  Peripheral blood  Simons Simplex Collection  Study to Explore Early Development Index. décimale : PER Périodiques Résumé : Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 x 10(- 7). Seven CpGs showed differences at p < 1 x 10(- 5) and 48 at 1 x 10(- 4). Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0224-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Case-control meta-analysis of blood DNA methylation and autism spectrum disorder [Texte imprimé et/ou numérique] / S. V. ANDREWS, Auteur ; B. SHEPPARD, Auteur ; G. C. WINDHAM, Auteur ; Laura A. SCHIEVE, Auteur ; Diana SCHENDEL, Auteur ; Lisa A. CROEN, Auteur ; P. CHOPRA, Auteur ; R. S. ALISCH, Auteur ; C. J. NEWSCHAFFER, Auteur ; S. T. WARREN, Auteur ; A. P. FEINBERG, Auteur ; M. D. FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur . - 40p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 40p. Mots-clés : Autism Spectrum Disorder/blood/genetics  Case-Control Studies  Child, Preschool  CpG Islands  DNA Methylation  Epigenesis, Genetic  Female  Genome-Wide Association Study  Humans  Male  Autism spectrum disorders  Epigenome  Peripheral blood  Simons Simplex Collection  Study to Explore Early Development Index. décimale : PER Périodiques Résumé : Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 x 10(- 7). Seven CpGs showed differences at p < 1 x 10(- 5) and 48 at 1 x 10(- 4). Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0224-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research / K. LYALL in Journal of Autism and Developmental Disorders, 51-7 (July 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-7 (July 2021) . - p.2241-2253 Titre : Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research Type de document : Texte imprimé et/ou numérique Auteurs : K. LYALL, Auteur ; M. HOSSEINI, Auteur ; Christine LADD-ACOSTA, Auteur ; X. NING, Auteur ; D. CATELLIER, Auteur ; John N. CONSTANTINO, Auteur ; Lisa A. CROEN, Auteur ; A. J. KAAT, Auteur ; Kelly N. BOTTERON, Auteur ; Nicole R. BUSH, Auteur ; Stephen R. DAGER, Auteur ; C. S. DUARTE, Auteur ; M. D. FALLIN, Auteur ; Heather C. HAZLETT, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; R. M. JOSEPH, Auteur ; Margaret R. KARAGAS, Auteur ; S. KORRICK, Auteur ; R. LANDA, Auteur ; D. MESSINGER, Auteur ; E. OKEN, Auteur ; S. OZONOFF, Auteur ; J. PIVEN, Auteur ; J. PANDEY, Auteur ; Sheela SATHYANARAYA, Auteur ; Robert T. SCHULTZ, Auteur ; T. ST JOHN, Auteur ; R. SCHMIDT, Auteur ; Heather E. VOLK, Auteur ; C. J. NEWSCHAFFER, Auteur Article en page(s) : p.2241-2253 Langues : Anglais (eng) Mots-clés : Adolescent  Area Under Curve  Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Communication  Female  Humans  Male  Psychiatric Status Rating Scales/standards  Psychometrics  Reproducibility of Results  Social Behavior  Autism spectrum disorder  Quantitative traits  Social Responsiveness Scale  Social communication Index. décimale : PER Périodiques Résumé : Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item "short" to 65-item "full" SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores. En ligne : http://dx.doi.org/10.1007/s10803-020-04667-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=452 [article] Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research [Texte imprimé et/ou numérique] / K. LYALL, Auteur ; M. HOSSEINI, Auteur ; Christine LADD-ACOSTA, Auteur ; X. NING, Auteur ; D. CATELLIER, Auteur ; John N. CONSTANTINO, Auteur ; Lisa A. CROEN, Auteur ; A. J. KAAT, Auteur ; Kelly N. BOTTERON, Auteur ; Nicole R. BUSH, Auteur ; Stephen R. DAGER, Auteur ; C. S. DUARTE, Auteur ; M. D. FALLIN, Auteur ; Heather C. HAZLETT, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; R. M. JOSEPH, Auteur ; Margaret R. KARAGAS, Auteur ; S. KORRICK, Auteur ; R. LANDA, Auteur ; D. MESSINGER, Auteur ; E. OKEN, Auteur ; S. OZONOFF, Auteur ; J. PIVEN, Auteur ; J. PANDEY, Auteur ; Sheela SATHYANARAYA, Auteur ; Robert T. SCHULTZ, Auteur ; T. ST JOHN, Auteur ; R. SCHMIDT, Auteur ; Heather E. VOLK, Auteur ; C. J. NEWSCHAFFER, Auteur . - p.2241-2253. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-7 (July 2021) . - p.2241-2253 Mots-clés : Adolescent  Area Under Curve  Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Communication  Female  Humans  Male  Psychiatric Status Rating Scales/standards  Psychometrics  Reproducibility of Results  Social Behavior  Autism spectrum disorder  Quantitative traits  Social Responsiveness Scale  Social communication Index. décimale : PER Périodiques Résumé : Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item "short" to 65-item "full" SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores. En ligne : http://dx.doi.org/10.1007/s10803-020-04667-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=452

Gastrointestinal Symptoms in 2- to 5-Year-Old Children in the Study to Explore Early Development / A. M. REYNOLDS in Journal of Autism and Developmental Disorders, 51-11 (November 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-11 (November 2021) . - p.3806-3817 Titre : Gastrointestinal Symptoms in 2- to 5-Year-Old Children in the Study to Explore Early Development Type de document : Texte imprimé et/ou numérique Auteurs : A. M. REYNOLDS, Auteur ; G. N. SOKE, Auteur ; Katherine R. SABOURIN, Auteur ; Lisa A. CROEN, Auteur ; Julie L. DANIELS, Auteur ; M. D. FALLIN, Auteur ; T. V. E. KRAL, Auteur ; L. C. LEE, Auteur ; C. J. NEWSCHAFFER, Auteur ; J. A. PINTO-MARTIN, Auteur ; Laura A. SCHIEVE, Auteur ; A. SIMS, Auteur ; Lisa D. WIGGINS, Auteur ; S. E. LEVY, Auteur Article en page(s) : p.3806-3817 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology  Autistic Disorder  Child  Child, Preschool  Developmental Disabilities/diagnosis/epidemiology  Gastrointestinal Diseases/diagnosis/epidemiology  Humans  Prevalence  Autism spectrum disorder  Developmental delay  Gastrointestinal  Preschool Index. décimale : PER Périodiques Résumé : Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n?=?672), with other developmental delays (DD)/(n?=?938), and children in the general population (POP)/(n?=?851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management. En ligne : http://dx.doi.org/10.1007/s10803-020-04786-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453 [article] Gastrointestinal Symptoms in 2- to 5-Year-Old Children in the Study to Explore Early Development [Texte imprimé et/ou numérique] / A. M. REYNOLDS, Auteur ; G. N. SOKE, Auteur ; Katherine R. SABOURIN, Auteur ; Lisa A. CROEN, Auteur ; Julie L. DANIELS, Auteur ; M. D. FALLIN, Auteur ; T. V. E. KRAL, Auteur ; L. C. LEE, Auteur ; C. J. NEWSCHAFFER, Auteur ; J. A. PINTO-MARTIN, Auteur ; Laura A. SCHIEVE, Auteur ; A. SIMS, Auteur ; Lisa D. WIGGINS, Auteur ; S. E. LEVY, Auteur . - p.3806-3817. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-11 (November 2021) . - p.3806-3817 Mots-clés : Autism Spectrum Disorder/epidemiology  Autistic Disorder  Child  Child, Preschool  Developmental Disabilities/diagnosis/epidemiology  Gastrointestinal Diseases/diagnosis/epidemiology  Humans  Prevalence  Autism spectrum disorder  Developmental delay  Gastrointestinal  Preschool Index. décimale : PER Périodiques Résumé : Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n?=?672), with other developmental delays (DD)/(n?=?938), and children in the general population (POP)/(n?=?851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management. En ligne : http://dx.doi.org/10.1007/s10803-020-04786-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453

Infant siblings and the investigation of autism risk factors / C. J. NEWSCHAFFER in Journal of Neurodevelopmental Disorders, 4-1 (December 2012)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 4-1 (December 2012) . - p.7 Titre : Infant siblings and the investigation of autism risk factors Type de document : Texte imprimé et/ou numérique Auteurs : C. J. NEWSCHAFFER, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; D. V. NGUYEN, Auteur ; N. L. LEE, Auteur ; C. A. BERRY, Auteur ; H. FARZADEGAN, Auteur ; H. N. HESS, Auteur ; R. J. LANDA, Auteur ; S. E. LEVY, Auteur ; M. L. MASSOLO, Auteur ; S. C. MEYERER, Auteur ; S. M. MOHAMMED, Auteur ; M. C. OLIVER, Auteur ; S. OZONOFF, Auteur ; J. PANDEY, Auteur ; A. SCHROEDER, Auteur ; K. M. SHEDD-WISE, Auteur Article en page(s) : p.7 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Infant sibling studies have been at the vanguard of autism spectrum disorders (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder. Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research. Moving targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study. This review considers the enriched-risk pregnancy cohort approach of studying infant siblings in the context of current thinking on ASD etiologic mechanisms. It then discusses the key features of this approach and provides a description of the design and implementation strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism Risk Longitudinal Investigation (EARLI). En ligne : http://dx.doi.org/10.1186/1866-1955-4-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=344 [article] Infant siblings and the investigation of autism risk factors [Texte imprimé et/ou numérique] / C. J. NEWSCHAFFER, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; D. V. NGUYEN, Auteur ; N. L. LEE, Auteur ; C. A. BERRY, Auteur ; H. FARZADEGAN, Auteur ; H. N. HESS, Auteur ; R. J. LANDA, Auteur ; S. E. LEVY, Auteur ; M. L. MASSOLO, Auteur ; S. C. MEYERER, Auteur ; S. M. MOHAMMED, Auteur ; M. C. OLIVER, Auteur ; S. OZONOFF, Auteur ; J. PANDEY, Auteur ; A. SCHROEDER, Auteur ; K. M. SHEDD-WISE, Auteur . - p.7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 4-1 (December 2012) . - p.7 Index. décimale : PER Périodiques Résumé : Infant sibling studies have been at the vanguard of autism spectrum disorders (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder. Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research. Moving targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study. This review considers the enriched-risk pregnancy cohort approach of studying infant siblings in the context of current thinking on ASD etiologic mechanisms. It then discusses the key features of this approach and provides a description of the design and implementation strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism Risk Longitudinal Investigation (EARLI). En ligne : http://dx.doi.org/10.1186/1866-1955-4-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=344

A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood / C. E. MORDAUNT in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 36 p. Titre : A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood Type de document : Texte imprimé et/ou numérique Auteurs : C. E. MORDAUNT, Auteur ; B. Y. PARK, Auteur ; K. M. BAKULSKI, Auteur ; J. I. FEINBERG, Auteur ; Lisa A. CROEN, Auteur ; Christine LADD-ACOSTA, Auteur ; C. J. NEWSCHAFFER, Auteur ; Heather E. VOLK, Auteur ; S. OZONOFF, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur ; Rebecca J. SCHMIDT, Auteur ; M. D. FALLIN, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Chromatin  Environment  Gene expression  Meta-analysis  Microarray  Neurodevelopment  Perinatal  Prospective study  Umbilical cord blood Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology. En ligne : http://dx.doi.org/10.1186/s13229-019-0287-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood [Texte imprimé et/ou numérique] / C. E. MORDAUNT, Auteur ; B. Y. PARK, Auteur ; K. M. BAKULSKI, Auteur ; J. I. FEINBERG, Auteur ; Lisa A. CROEN, Auteur ; Christine LADD-ACOSTA, Auteur ; C. J. NEWSCHAFFER, Auteur ; Heather E. VOLK, Auteur ; S. OZONOFF, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur ; Rebecca J. SCHMIDT, Auteur ; M. D. FALLIN, Auteur . - 36 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 36 p. Mots-clés : Autism spectrum disorder  Chromatin  Environment  Gene expression  Meta-analysis  Microarray  Neurodevelopment  Perinatal  Prospective study  Umbilical cord blood Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology. En ligne : http://dx.doi.org/10.1186/s13229-019-0287-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study / B. Y. PARK in Molecular Autism, 8 (2017)  

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