Centre d'Information et de documentation du CRA Rhône-Alpes
CRA
Informations pratiques
-
Adresse
Centre d'information et de documentation
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexHoraires
Lundi au Vendredi
9h00-12h00 13h30-16h00Contact
Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Résultat de la recherche
12 recherche sur le mot-clé 'Copy number variation'
Affiner la recherche Générer le flux rss de la recherche
Partager le résultat de cette recherche Faire une suggestion
The joint effect of air pollution exposure and copy number variation on risk for autism / Dokyoon KIM in Autism Research, 10-9 (September 2017)
[article]
Titre : The joint effect of air pollution exposure and copy number variation on risk for autism Type de document : Texte imprimé et/ou numérique Auteurs : Dokyoon KIM, Auteur ; Heather E. VOLK, Auteur ; Santhosh GIRIRAJAN, Auteur ; Sarah PENDERGRASS, Auteur ; Molly A. HALL, Auteur ; Shefali S. VERMA, Auteur ; Rebecca J. SCHMIDT, Auteur ; Robin L. HANSEN, Auteur ; Debashis GHOSH, Auteur ; Yunin LUDENA-RODRIGUEZ, Auteur ; Kyoungmi KIM, Auteur ; Marylyn D. RITCHIE, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Scott B. SELLECK, Auteur Article en page(s) : p.1470-1480 Langues : Anglais (eng) Mots-clés : autism copy number variation air pollution gene-environment interaction Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P?0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25–2.73) or ozone (OR 1.20, 95% CI 0.93–1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other. En ligne : http://dx.doi.org/10.1002/aur.1799 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=320
in Autism Research > 10-9 (September 2017) . - p.1470-1480[article] The joint effect of air pollution exposure and copy number variation on risk for autism [Texte imprimé et/ou numérique] / Dokyoon KIM, Auteur ; Heather E. VOLK, Auteur ; Santhosh GIRIRAJAN, Auteur ; Sarah PENDERGRASS, Auteur ; Molly A. HALL, Auteur ; Shefali S. VERMA, Auteur ; Rebecca J. SCHMIDT, Auteur ; Robin L. HANSEN, Auteur ; Debashis GHOSH, Auteur ; Yunin LUDENA-RODRIGUEZ, Auteur ; Kyoungmi KIM, Auteur ; Marylyn D. RITCHIE, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Scott B. SELLECK, Auteur . - p.1470-1480.
Langues : Anglais (eng)
in Autism Research > 10-9 (September 2017) . - p.1470-1480
Mots-clés : autism copy number variation air pollution gene-environment interaction Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child's CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P?0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25–2.73) or ozone (OR 1.20, 95% CI 0.93–1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other. En ligne : http://dx.doi.org/10.1002/aur.1799 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=320 Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation / M. J. GAZZELLONE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
[article]
Titre : Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation Type de document : Texte imprimé et/ou numérique Auteurs : M. J. GAZZELLONE, Auteur ; M. ZARREI, Auteur ; C. L. BURTON, Auteur ; S. WALKER, Auteur ; M. UDDIN, Auteur ; S. M. SHAHEEN, Auteur ; J. COSTE, Auteur ; R. RAJENDRAM, Auteur ; R. J. SCHACHTER, Auteur ; M. COLASANTO, Auteur ; G. L. HANNA, Auteur ; D. R. ROSENBERG, Auteur ; N. SORENI, Auteur ; K. D. FITZGERALD, Auteur ; C. R. MARSHALL, Auteur ; J. A. BUCHANAN, Auteur ; D. MERICO, Auteur ; P. D. ARNOLD, Auteur ; Stephen SCHERER, Auteur Article en page(s) : p.36 Langues : Anglais (eng) Mots-clés : Copy number variation Obsessive-compulsive disorder Pediatrics Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 x 10(-03); FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36[article] Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation [Texte imprimé et/ou numérique] / M. J. GAZZELLONE, Auteur ; M. ZARREI, Auteur ; C. L. BURTON, Auteur ; S. WALKER, Auteur ; M. UDDIN, Auteur ; S. M. SHAHEEN, Auteur ; J. COSTE, Auteur ; R. RAJENDRAM, Auteur ; R. J. SCHACHTER, Auteur ; M. COLASANTO, Auteur ; G. L. HANNA, Auteur ; D. R. ROSENBERG, Auteur ; N. SORENI, Auteur ; K. D. FITZGERALD, Auteur ; C. R. MARSHALL, Auteur ; J. A. BUCHANAN, Auteur ; D. MERICO, Auteur ; P. D. ARNOLD, Auteur ; Stephen SCHERER, Auteur . - p.36.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36
Mots-clés : Copy number variation Obsessive-compulsive disorder Pediatrics Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 x 10(-03); FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD. En ligne : http://dx.doi.org/10.1186/s11689-016-9170-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH) / Eloisa S. MOREIRA in Research in Autism Spectrum Disorders, 23 (March 2016)
[article]
Titre : Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH) Type de document : Texte imprimé et/ou numérique Auteurs : Eloisa S. MOREIRA, Auteur ; Isabela M. W. SILVA, Auteur ; Naila LOURENÇO, Auteur ; Danielle P. MOREIRA, Auteur ; Cintia M. RIBEIRO, Auteur ; Ana Luiza B. MARTINS, Auteur ; Karina GRIESI-OLIVEIRA, Auteur ; Monize LAZAR, Auteur ; Silvia S. COSTA, Auteur ; Michel S. NASLAVSKY, Auteur ; Kátia M. ROCHA, Auteur ; Meire AGUENA, Auteur ; Agnes C. FETT-CONTE, Auteur ; Mayana ZATZ, Auteur ; Carla ROSENBERG, Auteur ; Elaine C. ZACHI, Auteur ; Débora R. BERTOLA, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : p.145-151 Langues : Anglais (eng) Mots-clés : Autism Copy number variation Comparative genomic hybridization Neurodevelopmental disorder MBD2 SLC17A6 Index. décimale : PER Périodiques Résumé : Abstract Autism spectrum disorder (ASD) has a strong genetic basis and advances in genomic scanning methods have resulted in the identification of the underlying alterations in about 30% of the cases. The overwhelming majority of these alterations are either sequencing variants or large copy number variations (CNVs). In this pilot study, we tested whether the use of a customized array comparative genomic hybridization (aCGH), targeting exons of 269 ASD candidate genes, would allow the identification of small potentially pathogenic CNVs (<100 Kb). We detected 10 rare, potentially pathogenic CNVs in nine out of 98 patients with idiopathic ASD, and none of 200 Brazilian controls. Two out of five CNVs identified among the non-syndromic cases, involving the genes MBD2 and SLC17A6, were smaller than 100 Kb. In a subsequent screening of other 407 patients and 350 non-affected controls for CNVs involving SLC17A6, a gene without previous documentation in the literature of involvement with neurodevelopmental disorders, we found intragenic duplications in another proband but also in five controls. Of note, a commercial 500 K SNP-array did not detect the smallest gains in SLC17A6. Our results suggest that small CNVs contribute to the etiology of ASD and that customized CGH array has significant potential to improve the sensitivity for detecting this class of alterations. En ligne : http://dx.doi.org/10.1016/j.rasd.2015.12.012 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282
in Research in Autism Spectrum Disorders > 23 (March 2016) . - p.145-151[article] Detection of small copy number variations (CNVs) in autism spectrum disorder (ASD) by custom array comparative genomic hybridization (aCGH) [Texte imprimé et/ou numérique] / Eloisa S. MOREIRA, Auteur ; Isabela M. W. SILVA, Auteur ; Naila LOURENÇO, Auteur ; Danielle P. MOREIRA, Auteur ; Cintia M. RIBEIRO, Auteur ; Ana Luiza B. MARTINS, Auteur ; Karina GRIESI-OLIVEIRA, Auteur ; Monize LAZAR, Auteur ; Silvia S. COSTA, Auteur ; Michel S. NASLAVSKY, Auteur ; Kátia M. ROCHA, Auteur ; Meire AGUENA, Auteur ; Agnes C. FETT-CONTE, Auteur ; Mayana ZATZ, Auteur ; Carla ROSENBERG, Auteur ; Elaine C. ZACHI, Auteur ; Débora R. BERTOLA, Auteur ; Estevão VADASZ, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - p.145-151.
Langues : Anglais (eng)
in Research in Autism Spectrum Disorders > 23 (March 2016) . - p.145-151
Mots-clés : Autism Copy number variation Comparative genomic hybridization Neurodevelopmental disorder MBD2 SLC17A6 Index. décimale : PER Périodiques Résumé : Abstract Autism spectrum disorder (ASD) has a strong genetic basis and advances in genomic scanning methods have resulted in the identification of the underlying alterations in about 30% of the cases. The overwhelming majority of these alterations are either sequencing variants or large copy number variations (CNVs). In this pilot study, we tested whether the use of a customized array comparative genomic hybridization (aCGH), targeting exons of 269 ASD candidate genes, would allow the identification of small potentially pathogenic CNVs (<100 Kb). We detected 10 rare, potentially pathogenic CNVs in nine out of 98 patients with idiopathic ASD, and none of 200 Brazilian controls. Two out of five CNVs identified among the non-syndromic cases, involving the genes MBD2 and SLC17A6, were smaller than 100 Kb. In a subsequent screening of other 407 patients and 350 non-affected controls for CNVs involving SLC17A6, a gene without previous documentation in the literature of involvement with neurodevelopmental disorders, we found intragenic duplications in another proband but also in five controls. Of note, a commercial 500 K SNP-array did not detect the smallest gains in SLC17A6. Our results suggest that small CNVs contribute to the etiology of ASD and that customized CGH array has significant potential to improve the sensitivity for detecting this class of alterations. En ligne : http://dx.doi.org/10.1016/j.rasd.2015.12.012 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282 Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders / G. COSTAIN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)
[article]
Titre : Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : Adhd Autism Copy number variation Dmxl2 Grik5 Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p.[article] Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders [Texte imprimé et/ou numérique] / G. COSTAIN, Auteur ; S. WALKER, Auteur ; B. ARGIROPOULOS, Auteur ; D. A. BARIBEAU, Auteur ; A. S. BASSETT, Auteur ; E. BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; B. KELLAM, Auteur ; C. R. MARSHALL, Auteur ; A. PRASAD, Auteur ; M. A. SERRANO, Auteur ; D. J. STAVROPOULOS, Auteur ; H. TWEDE, Auteur ; J. R. VERMEESCH, Auteur ; J. A. S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur . - 3 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p.
Mots-clés : Adhd Autism Copy number variation Dmxl2 Grik5 Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank / Chloe X. YAP in Molecular Autism, 12 (2021)
[article]
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
in Molecular Autism > 12 (2021) . - 12p.[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 Mouse Models of 22q11.2-Associated Autism Spectrum Disorder / Noboru HIROI in Autism - Open Access, 2-S ([01/12/2012])
PermalinkA genotype resource for postmortem brain samples from the Autism Tissue Program / Richard F. WINTLE in Autism Research, 4-2 (April 2011)
PermalinkFurther Evidence for DLGAP2 as Strong Autism Spectrum Disorders/Intellectual Disability Candidate Gene / Hélène POQUET in Autism - Open Access, 7-1 ([01/01/2017])
PermalinkHyperactivity and male-specific sleep deficits in the 16p11.2 deletion mouse model of autism / Christopher C. ANGELAKOS in Autism Research, 10-4 (April 2017)
PermalinkTargeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models / Sandra MARTIN LORENZO in Molecular Autism, 12 (2021)
Permalink