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) . - 12p. Titre : Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank Type de document : Texte imprimé et/ou numérique 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 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) : 12p. 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 et/ou numérique] / 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 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 . - 12p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 12p. 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

Research Review: Polygenic methods and their application to psychiatric traits / Naomi R. WRAY in Journal of Child Psychology and Psychiatry, 55-10 (October 2014)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 55-10 (October 2014) . - p.1068-1087 Titre : Research Review: Polygenic methods and their application to psychiatric traits Type de document : Texte imprimé et/ou numérique Auteurs : Naomi R. WRAY, Auteur ; Sang Hong LEE, Auteur ; Divya MEHTA, Auteur ; Anna A. E. VINKHUYZEN, Auteur ; Frank DUDBRIDGE, Auteur ; Christel M. MIDDELDORP, Auteur Article en page(s) : p.1068-1087 Langues : Anglais (eng) Mots-clés : Polygenic risk scoring  genome-wide association studies  psychiatric disorders  heritability  SNP analyses  disease traits Index. décimale : PER Périodiques Résumé : Background Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. Methods and scope We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. Findings Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. Conclusions Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors. En ligne : http://dx.doi.org/10.1111/jcpp.12295 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=238 [article] Research Review: Polygenic methods and their application to psychiatric traits [Texte imprimé et/ou numérique] / Naomi R. WRAY, Auteur ; Sang Hong LEE, Auteur ; Divya MEHTA, Auteur ; Anna A. E. VINKHUYZEN, Auteur ; Frank DUDBRIDGE, Auteur ; Christel M. MIDDELDORP, Auteur . - p.1068-1087. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 55-10 (October 2014) . - p.1068-1087 Mots-clés : Polygenic risk scoring  genome-wide association studies  psychiatric disorders  heritability  SNP analyses  disease traits Index. décimale : PER Périodiques Résumé : Background Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. Methods and scope We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. Findings Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. Conclusions Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors. En ligne : http://dx.doi.org/10.1111/jcpp.12295 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=238

The Construction and Validation of an Abridged Version of the Autism-Spectrum Quotient (AQ-Short) / Rosa A. HOEKSTRA in Journal of Autism and Developmental Disorders, 41-5 (May 2011)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 41-5 (May 2011) . - p.589-596 Titre : The Construction and Validation of an Abridged Version of the Autism-Spectrum Quotient (AQ-Short) Type de document : Texte imprimé et/ou numérique Auteurs : Rosa A. HOEKSTRA, Auteur ; Anna A. E. VINKHUYZEN, Auteur ; Sally WHEELWRIGHT, Auteur ; Meike BARTELS, Auteur ; Dorret I. BOOMSMA, Auteur ; Simon BARON-COHEN, Auteur ; Daniëlle POSTHUMA, Auteur ; Sophie VAN DER SLUIS, Auteur Année de publication : 2011 Article en page(s) : p.589-596 Langues : Anglais (eng) Mots-clés : Autism  Factor analysis  Validity  Reliability  Autism phenotype  Autism-spectrum quotient Index. décimale : PER Périodiques Résumé : This study reports on the development and validation of an abridged version of the 50-item Autism-Spectrum Quotient (AQ), a self-report measure of autistic traits. We aimed to reduce the number of items whilst retaining high validity and a meaningful factor structure. The item reduction procedure was performed on data from 1,263 Dutch students and general population adults. The resulting 28-item AQ-Short was subsequently validated in 3 independent samples, both clinical and controls, from the Netherlands and the UK. The AQ-Short comprises two higher-order factors assessing ‘social behavioral difficulties’ and ‘a fascination for numbers/patterns’. The clear factor structure of the AQ-Short and its high sensitivity and specificity make the AQ-Short a useful alternative to the full 50-item version. En ligne : http://dx.doi.org/10.1007/s10803-010-1073-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121 [article] The Construction and Validation of an Abridged Version of the Autism-Spectrum Quotient (AQ-Short) [Texte imprimé et/ou numérique] / Rosa A. HOEKSTRA, Auteur ; Anna A. E. VINKHUYZEN, Auteur ; Sally WHEELWRIGHT, Auteur ; Meike BARTELS, Auteur ; Dorret I. BOOMSMA, Auteur ; Simon BARON-COHEN, Auteur ; Daniëlle POSTHUMA, Auteur ; Sophie VAN DER SLUIS, Auteur . - 2011 . - p.589-596. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 41-5 (May 2011) . - p.589-596 Mots-clés : Autism  Factor analysis  Validity  Reliability  Autism phenotype  Autism-spectrum quotient Index. décimale : PER Périodiques Résumé : This study reports on the development and validation of an abridged version of the 50-item Autism-Spectrum Quotient (AQ), a self-report measure of autistic traits. We aimed to reduce the number of items whilst retaining high validity and a meaningful factor structure. The item reduction procedure was performed on data from 1,263 Dutch students and general population adults. The resulting 28-item AQ-Short was subsequently validated in 3 independent samples, both clinical and controls, from the Netherlands and the UK. The AQ-Short comprises two higher-order factors assessing ‘social behavioral difficulties’ and ‘a fascination for numbers/patterns’. The clear factor structure of the AQ-Short and its high sensitivity and specificity make the AQ-Short a useful alternative to the full 50-item version. En ligne : http://dx.doi.org/10.1007/s10803-010-1073-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121

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