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

Prevalence of Motor Difficulties in Autism Spectrum Disorder: Analysis of a Population-Based Cohort / Melissa K. LICARI in Autism Research, 13-2 (February 2020)  

Public ISBD [article]  inAutism Research > 13-2 (February 2020) . - p.298-306 Titre : Prevalence of Motor Difficulties in Autism Spectrum Disorder: Analysis of a Population-Based Cohort Type de document : texte imprimé Auteurs : Melissa K. LICARI, Auteur ; Gail A. ALVARES, Auteur ; Kandice J. VARCIN, Auteur ; Kiah EVANS, Auteur ; Dominique CLEARY, Auteur ; Siobhan L. REID, Auteur ; Emma J. GLASSON, Auteur ; Keely BEBBINGTON, Auteur ; Jess E. REYNOLDS, Auteur ; John WRAY, Auteur ; Andrew J.O. WHITEHOUSE, Auteur Article en page(s) : p.298-306 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  developmental disabilities  motor disorders  motor skills  movement Index. décimale : PER Périodiques Résumé : Motor impairment is not currently included in the diagnostic criteria or evaluation of autism. This reflects the lack of large-scale studies demonstrating its prominence to advocate for change. We examined the prevalence of motor difficulties at the time of diagnosis in a large sample of children with autism utilizing standardized assessment, and the relationship between motor difficulties, core autism symptomology, and other prominent clinical features. Vineland Adaptive Behavior Scales were administered to children from the Western Australian Register for Autism Spectrum Disorders aged En ligne : http://dx.doi.org/10.1002/aur.2230 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420 [article] Prevalence of Motor Difficulties in Autism Spectrum Disorder: Analysis of a Population-Based Cohort [texte imprimé] / Melissa K. LICARI, Auteur ; Gail A. ALVARES, Auteur ; Kandice J. VARCIN, Auteur ; Kiah EVANS, Auteur ; Dominique CLEARY, Auteur ; Siobhan L. REID, Auteur ; Emma J. GLASSON, Auteur ; Keely BEBBINGTON, Auteur ; Jess E. REYNOLDS, Auteur ; John WRAY, Auteur ; Andrew J.O. WHITEHOUSE, Auteur . - p.298-306. Langues : Anglais (eng) in Autism Research > 13-2 (February 2020) . - p.298-306 Mots-clés : autism spectrum disorder  developmental disabilities  motor disorders  motor skills  movement Index. décimale : PER Périodiques Résumé : Motor impairment is not currently included in the diagnostic criteria or evaluation of autism. This reflects the lack of large-scale studies demonstrating its prominence to advocate for change. We examined the prevalence of motor difficulties at the time of diagnosis in a large sample of children with autism utilizing standardized assessment, and the relationship between motor difficulties, core autism symptomology, and other prominent clinical features. Vineland Adaptive Behavior Scales were administered to children from the Western Australian Register for Autism Spectrum Disorders aged En ligne : http://dx.doi.org/10.1002/aur.2230 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=420

Symptom severity in autism spectrum disorder is related to the frequency and severity of nausea and vomiting during pregnancy: a retrospective case-control study / Andrew J.O. WHITEHOUSE in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 37p. Titre : Symptom severity in autism spectrum disorder is related to the frequency and severity of nausea and vomiting during pregnancy: a retrospective case-control study Type de document : texte imprimé Auteurs : Andrew J.O. WHITEHOUSE, Auteur ; Gail A. ALVARES, Auteur ; Dominique CLEARY, Auteur ; Alexis HARUN, Auteur ; Angela STOJANOSKA, Auteur ; Lauren J. TAYLOR, Auteur ; Kandice J. VARCIN, Auteur ; Murray T. MAYBERY, Auteur Article en page(s) : 37p. Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/epidemiology  Case-Control Studies  Child  Child, Preschool  Female  Humans  Male  Morning Sickness/epidemiology  Nausea/epidemiology  Pregnancy Index. décimale : PER Périodiques Résumé : Background: Nausea and vomiting during pregnancy (NVP) is thought to be caused by changes in maternal hormones during pregnancy. Differences in hormone exposure during prenatal life have been implicated in the causal pathways for some cases of autism spectrum disorder (ASD). However, no study has investigated whether the presence and severity of NVP may be related to symptom severity in offspring with ASD. Methods: A large sample of children with ASD (227 males and 60 females, aged 2 to 18 years) received a clinical assessment, during which parents completed questionnaires regarding their child's social (Social Responsiveness Scale, SRS) and communication (Children's Communication Checklist-2nd edition, CCC-2) symptoms. Parents also reported on a 5-point scale the frequency and severity of NVPs during the pregnancy of the child being assessed: (1) no NVP during the pregnancy, (2) occasional nausea, but no vomiting, (3) daily nausea, but no vomiting, (4) occasional vomiting, with or without nausea, and (5) daily nausea and vomiting. Results: Impairments in social responsiveness in offspring, as indexed by SRS total score, significantly increased as a function of the frequency and severity of their mothers' NVP, as did the level of language difficulties as indexed by the Global Communication Composite of the CCC-2. Conclusions: The strong, positive association between increasing frequency and severity of NVP and ASD severity in offspring provides further evidence that exposure to an atypical hormonal environment during prenatal life may affect neurodevelopment and contribute to the ASD phenotype. Given that the measure of NVP symptoms in the current study was based on retrospective recall, replication of this finding is required before strong conclusions can be drawn. En ligne : https://dx.doi.org/10.1186/s13229-018-0223-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Symptom severity in autism spectrum disorder is related to the frequency and severity of nausea and vomiting during pregnancy: a retrospective case-control study [texte imprimé] / Andrew J.O. WHITEHOUSE, Auteur ; Gail A. ALVARES, Auteur ; Dominique CLEARY, Auteur ; Alexis HARUN, Auteur ; Angela STOJANOSKA, Auteur ; Lauren J. TAYLOR, Auteur ; Kandice J. VARCIN, Auteur ; Murray T. MAYBERY, Auteur . - 37p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 37p. Mots-clés : Adolescent  Autism Spectrum Disorder/epidemiology  Case-Control Studies  Child  Child, Preschool  Female  Humans  Male  Morning Sickness/epidemiology  Nausea/epidemiology  Pregnancy Index. décimale : PER Périodiques Résumé : Background: Nausea and vomiting during pregnancy (NVP) is thought to be caused by changes in maternal hormones during pregnancy. Differences in hormone exposure during prenatal life have been implicated in the causal pathways for some cases of autism spectrum disorder (ASD). However, no study has investigated whether the presence and severity of NVP may be related to symptom severity in offspring with ASD. Methods: A large sample of children with ASD (227 males and 60 females, aged 2 to 18 years) received a clinical assessment, during which parents completed questionnaires regarding their child's social (Social Responsiveness Scale, SRS) and communication (Children's Communication Checklist-2nd edition, CCC-2) symptoms. Parents also reported on a 5-point scale the frequency and severity of NVPs during the pregnancy of the child being assessed: (1) no NVP during the pregnancy, (2) occasional nausea, but no vomiting, (3) daily nausea, but no vomiting, (4) occasional vomiting, with or without nausea, and (5) daily nausea and vomiting. Results: Impairments in social responsiveness in offspring, as indexed by SRS total score, significantly increased as a function of the frequency and severity of their mothers' NVP, as did the level of language difficulties as indexed by the Global Communication Composite of the CCC-2. Conclusions: The strong, positive association between increasing frequency and severity of NVP and ASD severity in offspring provides further evidence that exposure to an atypical hormonal environment during prenatal life may affect neurodevelopment and contribute to the ASD phenotype. Given that the measure of NVP symptoms in the current study was based on retrospective recall, replication of this finding is required before strong conclusions can be drawn. En ligne : https://dx.doi.org/10.1186/s13229-018-0223-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

The misnomer of 'high functioning autism': Intelligence is an imprecise predictor of functional abilities at diagnosis / Gail A. ALVARES in Autism, 24-1 (January 2020)  

Public ISBD [article]  inAutism > 24-1 (January 2020) . - p.221-232 Titre : The misnomer of 'high functioning autism': Intelligence is an imprecise predictor of functional abilities at diagnosis Type de document : texte imprimé Auteurs : Gail A. ALVARES, Auteur ; Keely BEBBINGTON, Auteur ; Dominique CLEARY, Auteur ; Kiah EVANS, Auteur ; Emma J. GLASSON, Auteur ; Murray T. MAYBERY, Auteur ; Sarah PILLAR, Auteur ; Mirko ULJAREVIĆ, Auteur ; Kandice J. VARCIN, Auteur ; John WRAY, Auteur ; Andrew J.O. WHITEHOUSE, Auteur Article en page(s) : p.221-232 Langues : Anglais (eng) Mots-clés : adaptive behaviour  autism spectrum disorders  cognitive impairment  intellectual disability Index. décimale : PER Périodiques Résumé : 'High functioning autism' is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants (n = 2225, 1-18 years of age) were notified at diagnosis to a prospective register and grouped by presence (n = 1041) or absence (n = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group's adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that 'high functioning autism' is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice. En ligne : http://dx.doi.org/10.1177/1362361319852831 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] The misnomer of 'high functioning autism': Intelligence is an imprecise predictor of functional abilities at diagnosis [texte imprimé] / Gail A. ALVARES, Auteur ; Keely BEBBINGTON, Auteur ; Dominique CLEARY, Auteur ; Kiah EVANS, Auteur ; Emma J. GLASSON, Auteur ; Murray T. MAYBERY, Auteur ; Sarah PILLAR, Auteur ; Mirko ULJAREVIĆ, Auteur ; Kandice J. VARCIN, Auteur ; John WRAY, Auteur ; Andrew J.O. WHITEHOUSE, Auteur . - p.221-232. Langues : Anglais (eng) in Autism > 24-1 (January 2020) . - p.221-232 Mots-clés : adaptive behaviour  autism spectrum disorders  cognitive impairment  intellectual disability Index. décimale : PER Périodiques Résumé : 'High functioning autism' is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants (n = 2225, 1-18 years of age) were notified at diagnosis to a prospective register and grouped by presence (n = 1041) or absence (n = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group's adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that 'high functioning autism' is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice. En ligne : http://dx.doi.org/10.1177/1362361319852831 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

---

1 (1 - 4 / 4) Par page : 25 50 100 200