2 recherche sur le mot-clé 'Autism Spectrum Disorder/genetics/diagnostic imaging'

Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder / Ohad REGEV in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Ohad REGEV, Auteur ; Apurba SHIL, Auteur ; Tal BRONSHTEIN, Auteur ; Amnon HADAR, Auteur ; Gal MEIRI, Auteur ; Dikla ZIGDON, Auteur ; Analya MICHAELOVSKI, Auteur ; Reli HERSHKOVITZ, Auteur ; Idan MENASHE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics/diagnostic imaging  Female  Male  Ultrasonography, Prenatal  Child  Exome Sequencing  Pregnancy  Cross-Sectional Studies  Child, Preschool  Genetic Variation  Genetic Predisposition to Disease  Autism spectrum disorder  Congenital anomalies  Fetal development  Genetic mutations  Prenatal ultrasound  Ultrasonography fetal anomalies  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. METHODS: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. RESULTS: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). CONCLUSIONS: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development. En ligne : https://dx.doi.org/10.1186/s11689-024-09573-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Association between rare, genetic variants linked to autism and ultrasonography fetal anomalies in children with autism spectrum disorder [texte imprimé] / Ohad REGEV, Auteur ; Apurba SHIL, Auteur ; Tal BRONSHTEIN, Auteur ; Amnon HADAR, Auteur ; Gal MEIRI, Auteur ; Dikla ZIGDON, Auteur ; Analya MICHAELOVSKI, Auteur ; Reli HERSHKOVITZ, Auteur ; Idan MENASHE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Autism Spectrum Disorder/genetics/diagnostic imaging  Female  Male  Ultrasonography, Prenatal  Child  Exome Sequencing  Pregnancy  Cross-Sectional Studies  Child, Preschool  Genetic Variation  Genetic Predisposition to Disease  Autism spectrum disorder  Congenital anomalies  Fetal development  Genetic mutations  Prenatal ultrasound  Ultrasonography fetal anomalies  Whole-exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent evidence suggests that certain fetal anomalies detected upon prenatal ultrasound screenings are associated with autism spectrum disorder (ASD). In this cross-sectional study, we aimed to identify genetic variants associated with fetal ultrasound anomalies (UFAs) in children with ASD. METHODS: The study included all children with ASD who are registered in the database of the Azrieli National Center of Autism and Neurodevelopment and for whom both prenatal ultrasound and whole exome sequencing (WES) data were available. We applied our in-house integrative bioinformatics pipeline, AutScore, to these WES data to prioritize rare, gene-disrupting variants (GDVs) probably contributing to ASD susceptibily. Univariate statistics and multivariable regression were used to assess the associations between UFAs and GDVs identified in these children. RESULTS: The study sample comprised 126 children, of whom 43 (34.1%) had at least one UFA detected in the prenatal ultrasound scan. A total of 87 candidate ASD genetic variants were detected in 60 children, with 24 (40%) children carrying multiple variants. Children with UFAs were more likely to have loss-of-function (LoF) mutations (aOR = 2.55, 95%CI: 1.13-5.80). This association was particularly noticeable when children with structural anomalies or children with UFAs in their head and brain scans were compared to children without UFAs (any mutation: aOR = 8.28, 95%CI: 2.29-30.01; LoF: aOR = 5.72, 95%CI: 2.08-15.71 and any mutation: aOR = 6.39, 95%CI: 1.34-30.47; LoF: aOR = 4.50, 95%CI: 1.32-15.35, respectively). GDVs associated with UFAs were enriched in genes highly expressed across all tissues (aOR = 2.76, 95%CI: 1.14-6.68). There was a weak, but significant, correlation between the number of mutations and the number of abnormalities detected in the same children (r = 0.21, P = 0.016). CONCLUSIONS: The results provide valuable insights into the potential genetic basis of prenatal organogenesis abnormalities associated with ASD and shed light on the complex interplay between genetic factors and fetal development. En ligne : https://dx.doi.org/10.1186/s11689-024-09573-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults / Salahuddin MOHAMMAD in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 34p. Titre : Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults Type de document : texte imprimé Auteurs : Salahuddin MOHAMMAD, Auteur ; Mélissa GENTREAU, Auteur ; Manon DUBOL, Auteur ; Gull RUKH, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur Article en page(s) : 34p. Langues : Anglais (eng) Mots-clés : Humans  Cerebellum/diagnostic imaging/pathology  Brain Stem/diagnostic imaging/pathology  Magnetic Resonance Imaging  Male  Female  Phenotype  Adult  Multifactorial Inheritance  Genetic Predisposition to Disease  Organ Size  Middle Aged  Autistic Disorder/genetics/diagnostic imaging  Genome-Wide Association Study  Autism Spectrum Disorder/genetics/diagnostic imaging  Gray Matter/diagnostic imaging/pathology  Case-Control Studies  Autism  Brain MRI  Brainstem  Cerebellum  Polygenic risk score Index. décimale : PER Périodiques Résumé : Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~ 31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain. En ligne : https://dx.doi.org/10.1186/s13229-024-00611-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults [texte imprimé] / Salahuddin MOHAMMAD, Auteur ; Mélissa GENTREAU, Auteur ; Manon DUBOL, Auteur ; Gull RUKH, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur . - 34p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 34p. Mots-clés : Humans  Cerebellum/diagnostic imaging/pathology  Brain Stem/diagnostic imaging/pathology  Magnetic Resonance Imaging  Male  Female  Phenotype  Adult  Multifactorial Inheritance  Genetic Predisposition to Disease  Organ Size  Middle Aged  Autistic Disorder/genetics/diagnostic imaging  Genome-Wide Association Study  Autism Spectrum Disorder/genetics/diagnostic imaging  Gray Matter/diagnostic imaging/pathology  Case-Control Studies  Autism  Brain MRI  Brainstem  Cerebellum  Polygenic risk score Index. décimale : PER Périodiques Résumé : Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~ 31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain. En ligne : https://dx.doi.org/10.1186/s13229-024-00611-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538