512 recherche sur le mot-clé 'genetics'

Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome / Nycole A. COPPING in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 9p. Titre : Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome Type de document : texte imprimé Auteurs : Nycole A. COPPING, Auteur ; Jill L. SILVERMAN, Auteur Article en page(s) : 9p. Langues : Anglais (eng) Mots-clés : Angelman Syndrome  Behavior  Genetics  Mouse models  Seizures  Sleep  Spindles  Ube3a Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal-specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (> 80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS. METHODS: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light-dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice. RESULTS: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model. LIMITATIONS: This study was limited to the exon 2 deletion mouse model, and future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior. CONCLUSIONS: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing. En ligne : http://dx.doi.org/10.1186/s13229-021-00416-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome [texte imprimé] / Nycole A. COPPING, Auteur ; Jill L. SILVERMAN, Auteur . - 9p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 9p. Mots-clés : Angelman Syndrome  Behavior  Genetics  Mouse models  Seizures  Sleep  Spindles  Ube3a Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal-specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (> 80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS. METHODS: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light-dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice. RESULTS: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model. LIMITATIONS: This study was limited to the exon 2 deletion mouse model, and future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior. CONCLUSIONS: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing. En ligne : http://dx.doi.org/10.1186/s13229-021-00416-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Aetiological overlap between anxiety and attention deficit hyperactivity symptom dimensions in adolescence / Giorgia MICHELINI in Journal of Child Psychology and Psychiatry, 56-4 (April 2015)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 56-4 (April 2015) . - p.423-431 Titre : Aetiological overlap between anxiety and attention deficit hyperactivity symptom dimensions in adolescence Type de document : texte imprimé Auteurs : Giorgia MICHELINI, Auteur ; Thalia C. ELEY, Auteur ; Alice M. GREGORY, Auteur ; Tom A. MCADAMS, Auteur Article en page(s) : p.423-431 Langues : Anglais (eng) Mots-clés : Anxiety  ADH problems  genetics  twins  adolescence Index. décimale : PER Périodiques Résumé : Background Anxiety and attention-deficit/hyperactivity (ADH) problems are common in adolescence, often co-occur, and are characterised by high heterogeneity in their phenotypic expressions. Although it is known that anxiety and ADH problems correlate, the relationships between subtypes of anxiety and ADH problems have been scarcely investigated. Methods Using a large population sample of adolescent twins and siblings we explored the phenotypic and aetiological association between anxiety subtypes (panic/agoraphobia, separation anxiety, social anxiety, physical injury fears, obsessive-compulsive symptoms and generalised anxiety) and the two ADH dimensions (attention problems and hyperactivity/impulsivity). Both phenotypes were assessed using self-report questionnaires. Results The association between ADH problems and anxiety could be entirely attributed to attention problems, not hyperactivity/impulsivity. Most of the correlations between anxiety subtypes and attention problems showed an approximately equal role of genetic and nonshared environmental factors. Conclusions The high heterogeneity within anxiety and ADH problems should be taken into account in order to better understand comorbidity between them. En ligne : http://dx.doi.org/10.1111/jcpp.12318 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=260 [article] Aetiological overlap between anxiety and attention deficit hyperactivity symptom dimensions in adolescence [texte imprimé] / Giorgia MICHELINI, Auteur ; Thalia C. ELEY, Auteur ; Alice M. GREGORY, Auteur ; Tom A. MCADAMS, Auteur . - p.423-431. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 56-4 (April 2015) . - p.423-431 Mots-clés : Anxiety  ADH problems  genetics  twins  adolescence Index. décimale : PER Périodiques Résumé : Background Anxiety and attention-deficit/hyperactivity (ADH) problems are common in adolescence, often co-occur, and are characterised by high heterogeneity in their phenotypic expressions. Although it is known that anxiety and ADH problems correlate, the relationships between subtypes of anxiety and ADH problems have been scarcely investigated. Methods Using a large population sample of adolescent twins and siblings we explored the phenotypic and aetiological association between anxiety subtypes (panic/agoraphobia, separation anxiety, social anxiety, physical injury fears, obsessive-compulsive symptoms and generalised anxiety) and the two ADH dimensions (attention problems and hyperactivity/impulsivity). Both phenotypes were assessed using self-report questionnaires. Results The association between ADH problems and anxiety could be entirely attributed to attention problems, not hyperactivity/impulsivity. Most of the correlations between anxiety subtypes and attention problems showed an approximately equal role of genetic and nonshared environmental factors. Conclusions The high heterogeneity within anxiety and ADH problems should be taken into account in order to better understand comorbidity between them. En ligne : http://dx.doi.org/10.1111/jcpp.12318 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=260

An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure / Jane SUMMERS in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure Type de document : texte imprimé Auteurs : Jane SUMMERS, Auteur ; Danielle BARIBEAU, Auteur ; Polina PERLMAN, Auteur ; Ny HOANG, Auteur ; Sunny CUI, Auteur ; Aneta KRAKOWSKI, Auteur ; Patricia AMBROZEWICZ, Auteur ; Ariel HO, Auteur ; Thanuja SELVANAYAGAM, Auteur ; Kinga A. SÁNDOR-BAJUSZ, Auteur ; Katrina PALAD, Auteur ; Nishi PATEL, Auteur ; Sarah MCGAUGHEY, Auteur ; Louise GALLAGHER, Auteur ; Stephen W. SCHERER, Auteur ; Peter SZATMARI, Auteur ; Jacob VORSTMAN, Auteur Langues : Anglais (eng) Mots-clés : Humans  Child  Neurodevelopmental Disorders/genetics  Female  Male  Mental Disorders/genetics  Genetic Predisposition to Disease  Adolescent  Genetic disorder  Genetics  Interdisciplinary clinic  Mental health  Neurodevelopmental disorder  Psychiatry  Psychology  Research framework  speaker fees for Henry Stewart Talks Ltd. S.W.S. is on the Scientific Advisory  Committee of Population Bio, Deep Genomics, and serves as a Highly Cited Academic  Advisor for King Abdulaziz University. Intellectual property from aspects of his  research held at The Hospital for Sick Children are licensed to Athena  Diagnostics and Population Bio. D.B. has received research funding from MapLight  therapeutics. These relationships did not influence content of this manuscript  but are disclosed for potential future considerations. Index. décimale : PER Périodiques Résumé : BACKGROUND: A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary 'genetic-diagnosis-first' clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians. METHODS: We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians. RESULTS: 159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement. CONCLUSIONS: DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population. En ligne : https://dx.doi.org/10.1186/s11689-024-09552-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure [texte imprimé] / Jane SUMMERS, Auteur ; Danielle BARIBEAU, Auteur ; Polina PERLMAN, Auteur ; Ny HOANG, Auteur ; Sunny CUI, Auteur ; Aneta KRAKOWSKI, Auteur ; Patricia AMBROZEWICZ, Auteur ; Ariel HO, Auteur ; Thanuja SELVANAYAGAM, Auteur ; Kinga A. SÁNDOR-BAJUSZ, Auteur ; Katrina PALAD, Auteur ; Nishi PATEL, Auteur ; Sarah MCGAUGHEY, Auteur ; Louise GALLAGHER, Auteur ; Stephen W. SCHERER, Auteur ; Peter SZATMARI, Auteur ; Jacob VORSTMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Child  Neurodevelopmental Disorders/genetics  Female  Male  Mental Disorders/genetics  Genetic Predisposition to Disease  Adolescent  Genetic disorder  Genetics  Interdisciplinary clinic  Mental health  Neurodevelopmental disorder  Psychiatry  Psychology  Research framework  speaker fees for Henry Stewart Talks Ltd. S.W.S. is on the Scientific Advisory  Committee of Population Bio, Deep Genomics, and serves as a Highly Cited Academic  Advisor for King Abdulaziz University. Intellectual property from aspects of his  research held at The Hospital for Sick Children are licensed to Athena  Diagnostics and Population Bio. D.B. has received research funding from MapLight  therapeutics. These relationships did not influence content of this manuscript  but are disclosed for potential future considerations. Index. décimale : PER Périodiques Résumé : BACKGROUND: A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary 'genetic-diagnosis-first' clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians. METHODS: We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians. RESULTS: 159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement. CONCLUSIONS: DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population. En ligne : https://dx.doi.org/10.1186/s11689-024-09552-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

An Observational Study of Social Interaction Skills and Behaviors in Cornelia de Lange, Fragile X and Rubinstein-Taybi Syndromes / Katherine ELLIS in Journal of Autism and Developmental Disorders, 50-11 (November 2020)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 50-11 (November 2020) . - p.4001-4010 Titre : An Observational Study of Social Interaction Skills and Behaviors in Cornelia de Lange, Fragile X and Rubinstein-Taybi Syndromes Type de document : texte imprimé Auteurs : Katherine ELLIS, Auteur ; Chris OLIVER, Auteur ; Chrysi STEFANIDOU, Auteur ; Ian APPERLY, Auteur ; Jo MOSS, Auteur Article en page(s) : p.4001-4010 Langues : Anglais (eng) Mots-clés : Eye gaze  Fragile X syndrome  Genetics behavioural  Neurodevelopmental disorders  Social behavior Index. décimale : PER Périodiques Résumé : We directly assessed the broader aspects of sociability (social enjoyment, social motivation, social interaction skills and social discomfort) in individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and their association with autism characteristics and chronological age in these groups. Individuals with FXS (p < 0.01) and RTS (p < 0.01) showed poorer quality of eye contact compared to individuals with CdLS. Individuals with FXS showed less person and more object attention than individuals with CdLS (p < 0.01). Associations between sociability and autism characteristics and chronological age differed between groups, which may indicate divergence in the development and aetiology of different components of sociability across these groups. Findings indicate that individuals with CdLS, FXS and RTS show unique profiles of sociability. En ligne : http://dx.doi.org/10.1007/s10803-020-04440-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432 [article] An Observational Study of Social Interaction Skills and Behaviors in Cornelia de Lange, Fragile X and Rubinstein-Taybi Syndromes [texte imprimé] / Katherine ELLIS, Auteur ; Chris OLIVER, Auteur ; Chrysi STEFANIDOU, Auteur ; Ian APPERLY, Auteur ; Jo MOSS, Auteur . - p.4001-4010. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 50-11 (November 2020) . - p.4001-4010 Mots-clés : Eye gaze  Fragile X syndrome  Genetics behavioural  Neurodevelopmental disorders  Social behavior Index. décimale : PER Périodiques Résumé : We directly assessed the broader aspects of sociability (social enjoyment, social motivation, social interaction skills and social discomfort) in individuals with Cornelia de Lange (CdLS), fragile X (FXS) and Rubinstein-Taybi syndromes (RTS), and their association with autism characteristics and chronological age in these groups. Individuals with FXS (p < 0.01) and RTS (p < 0.01) showed poorer quality of eye contact compared to individuals with CdLS. Individuals with FXS showed less person and more object attention than individuals with CdLS (p < 0.01). Associations between sociability and autism characteristics and chronological age differed between groups, which may indicate divergence in the development and aetiology of different components of sociability across these groups. Findings indicate that individuals with CdLS, FXS and RTS show unique profiles of sociability. En ligne : http://dx.doi.org/10.1007/s10803-020-04440-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432

Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank / Chloe X. YAP in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 12 p. Titre : Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank Type de document : texte imprimé Auteurs : Chloe X. YAP, Auteur ; Gail A. ALVARES, Auteur ; Anjali K. HENDERS, Auteur ; Tian LIN, Auteur ; Leanne WALLACE, Auteur ; Alaina FARRELLY, Auteur ; Tiana MCLAREN, Auteur ; Jolene BERRY, Auteur ; Anna A.E. VINKHUYZEN, Auteur ; Maciej TRZASKOWSKI, Auteur ; Jian ZENG, Auteur ; Yuanhao YANG, Auteur ; Dominique CLEARY, Auteur ; Rachel GROVE, Auteur ; Claire HAFEKOST, Auteur ; Alexis HARUN, Auteur ; Helen HOLDSWORTH, Auteur ; Rachel JELLETT, Auteur ; Feroza KHAN, Auteur ; Lauren P. LAWSON, Auteur ; Jodie LESLIE, Auteur ; Mira LEVIS FRENK, Auteur ; Anne MASI, Auteur ; Nisha E. MATHEW, Auteur ; Melanie MUNIANDY, Auteur ; Michaela NOTHARD, Auteur ; Peter M. VISSCHER, Auteur ; Paul A. DAWSON, Auteur ; Cheryl DISSANAYAKE, Auteur ; Valsamma EAPEN, Auteur ; Helen S. HEUSSLER, Auteur ; Andrew J.O. WHITEHOUSE, Auteur ; Naomi R. WRAY, Auteur ; Jacob GRATTEN, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Australian autism biobank  Autism spectrum disorder  Copy number variation  Genetics  Polygenic score Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. METHODS: Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. RESULTS: The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. LIMITATIONS: This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. CONCLUSIONS: We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair). En ligne : http://dx.doi.org/10.1186/s13229-020-00407-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank [texte imprimé] / Chloe X. YAP, Auteur ; Gail A. ALVARES, Auteur ; Anjali K. HENDERS, Auteur ; Tian LIN, Auteur ; Leanne WALLACE, Auteur ; Alaina FARRELLY, Auteur ; Tiana MCLAREN, Auteur ; Jolene BERRY, Auteur ; Anna A.E. VINKHUYZEN, Auteur ; Maciej TRZASKOWSKI, Auteur ; Jian ZENG, Auteur ; Yuanhao YANG, Auteur ; Dominique CLEARY, Auteur ; Rachel GROVE, Auteur ; Claire HAFEKOST, Auteur ; Alexis HARUN, Auteur ; Helen HOLDSWORTH, Auteur ; Rachel JELLETT, Auteur ; Feroza KHAN, Auteur ; Lauren P. LAWSON, Auteur ; Jodie LESLIE, Auteur ; Mira LEVIS FRENK, Auteur ; Anne MASI, Auteur ; Nisha E. MATHEW, Auteur ; Melanie MUNIANDY, Auteur ; Michaela NOTHARD, Auteur ; Peter M. VISSCHER, Auteur ; Paul A. DAWSON, Auteur ; Cheryl DISSANAYAKE, Auteur ; Valsamma EAPEN, Auteur ; Helen S. HEUSSLER, Auteur ; Andrew J.O. WHITEHOUSE, Auteur ; Naomi R. WRAY, Auteur ; Jacob GRATTEN, Auteur . - 12 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 12 p. Mots-clés : Australian autism biobank  Autism spectrum disorder  Copy number variation  Genetics  Polygenic score Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. METHODS: Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. RESULTS: The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. LIMITATIONS: This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. CONCLUSIONS: We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair). En ligne : http://dx.doi.org/10.1186/s13229-020-00407-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Annual Research Review: Discovery science strategies in studies of the pathophysiology of child and adolescent psychiatric disorders - promises and limitations / Yihong ZHAO in Journal of Child Psychology and Psychiatry, 57-3 (March 2016)  

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Annual Research Review: Early conduct problems – precursors, outcomes, and etiology / Luke W. HYDE in Journal of Child Psychology and Psychiatry, 67-4 (April 2026)  

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Annual Research Review: Impact of advances in genetics in understanding developmental psychopathology / Anjene M. ADDINGTON in Journal of Child Psychology and Psychiatry, 53-5 (May 2012)  

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Annual Research Review: The (epi)genetics of neurodevelopmental disorders in the era of whole-genome sequencing – unveiling the dark matter / Dominik P. KISER in Journal of Child Psychology and Psychiatry, 56-3 (March 2015)  

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Annual Research Review: The role of the environment in the developmental psychopathology of autism spectrum condition / William MANDY in Journal of Child Psychology and Psychiatry, 57-3 (March 2016)  

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