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)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 3p. Titre : Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Type de document : Texte imprimé et/ou numérique Auteurs : B. Y. PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; J. A. KEELAN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; O. MONTGOMERY, Auteur ; C. J. NEWSCHAFFER, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Adult  Androstenedione/*metabolism  Autism Spectrum Disorder/metabolism/*psychology  Chromatography, Liquid  Cohort Studies  Dehydroepiandrosterone/*metabolism  Female  Fetal Blood/*metabolism  Humans  Infant  Linear Models  Longitudinal Studies  Male  Pregnancy  Prospective Studies  Risk Assessment  Severity of Illness Index  Siblings/*psychology  Tandem Mass Spectrometry  Testosterone/*metabolism  *Autism  *Sex difference  *Sibling  *Testosterone  *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study [Texte imprimé et/ou numérique] / B. Y. PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; J. A. KEELAN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; O. MONTGOMERY, Auteur ; C. J. NEWSCHAFFER, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 3p. Mots-clés : Adult  Androstenedione/*metabolism  Autism Spectrum Disorder/metabolism/*psychology  Chromatography, Liquid  Cohort Studies  Dehydroepiandrosterone/*metabolism  Female  Fetal Blood/*metabolism  Humans  Infant  Linear Models  Longitudinal Studies  Male  Pregnancy  Prospective Studies  Risk Assessment  Severity of Illness Index  Siblings/*psychology  Tandem Mass Spectrometry  Testosterone/*metabolism  *Autism  *Sex difference  *Sibling  *Testosterone  *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

---

1 (1 - 2 / 2)