14 recherche sur le mot-clé 'genotype'

Altered medial prefrontal cortex and dorsal raphé activity predict genotype and correlate with abnormal learning behavior in a mouse model of autism-associated 2p16.3 deletion / Rebecca B. HUGHES in Autism Research, 15-4 (April 2022)  

Public ISBD [article]  inAutism Research > 15-4 (April 2022) . - p.614-627 Titre : Altered medial prefrontal cortex and dorsal raphé activity predict genotype and correlate with abnormal learning behavior in a mouse model of autism-associated 2p16.3 deletion Type de document : texte imprimé Auteurs : Rebecca B. HUGHES, Auteur ; Jayde WHITTINGHAM-DOWD, Auteur ; Steven J. CLAPCOTE, Auteur ; Susan J. BROUGHTON, Auteur ; Neil DAWSON, Auteur Article en page(s) : p.614-627 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/genetics  Autistic Disorder  Disease Models, Animal  Dorsal Raphe Nucleus  Genotype  Humans  Male  Mice  Prefrontal Cortex/diagnostic imaging  Reversal Learning  cognitive neuroscience  copy number variation/copy number variants  frontal lobe  genotype-phenotype correlation  imaging genetics  mouse models  serotonin Index. décimale : PER Périodiques Résumé : 2p16.3 deletion, involving NEUREXIN1 (NRXN1) heterozygous deletion, substantially increases the risk of developing autism and other neurodevelopmental disorders. We have a poor understanding of how NRXN1 heterozygosity impacts on brain function and cognition to increase the risk of developing the disorder. Here we characterize the impact of Nrxn1 heterozygosity on cerebral metabolism, in mice, using (14) C-2-deoxyglucose imaging. We also assess performance in an olfactory-based discrimination and reversal learning (OB-DaRL) task and locomotor activity. We use decision tree classifiers to test the predictive relationship between cerebral metabolism and Nrxn1 genotype. Our data show that Nrxn1 heterozygosity induces prefrontal cortex (medial prelimbic cortex, mPrL) hypometabolism and a contrasting dorsal raphé nucleus (DRN) hypermetabolism. Metabolism in these regions allows for the predictive classification of Nrxn1 genotype. Consistent with reduced mPrL glucose utilization, prefrontal cortex insulin receptor signaling is decreased in Nrxn1 (+/-) mice. Behaviorally, Nrxn1 (+/-) mice show enhanced learning of a novel discrimination, impaired reversal learning and an increased latency to make correct choices. In addition, male Nrxn1 (+/-) mice show hyperlocomotor activity. Correlative analysis suggests that mPrL hypometabolism contributes to the enhanced novel odor discrimination seen in Nrxn1 (+/-) mice, while DRN hypermetabolism contributes to their increased latency in making correct choices. The data show that Nrxn1 heterozygosity impacts on prefrontal cortex and serotonin system function, which contribute to the cognitive alterations seen in these animals. The data suggest that Nrxn1 (+/-) mice provide a translational model for the cognitive and behavioral alterations seen in autism and other neurodevelopmental disorders associated with 2p16.3 deletion. LAY SUMMARY: Deletion of the chromosomal region 2p16.3, involving reduced NEUREXIN1 gene expression, dramatically increases the risk of developing autism. Here, we show that reduced Neurexin1 expression, in mice, impacts on the prefrontal cortex and impairs cognitive flexibility. The data suggest that 2p16.3 deletion increases the risk of developing autism by impacting on the prefrontal cortex. Mice with the deletion are a useful model for testing new drugs to treat the cognitive flexibility problems experienced by people with autism. En ligne : https://dx.doi.org/10.1002/aur.2685 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473 [article] Altered medial prefrontal cortex and dorsal raphé activity predict genotype and correlate with abnormal learning behavior in a mouse model of autism-associated 2p16.3 deletion [texte imprimé] / Rebecca B. HUGHES, Auteur ; Jayde WHITTINGHAM-DOWD, Auteur ; Steven J. CLAPCOTE, Auteur ; Susan J. BROUGHTON, Auteur ; Neil DAWSON, Auteur . - p.614-627. Langues : Anglais (eng) in Autism Research > 15-4 (April 2022) . - p.614-627 Mots-clés : Animals  Autism Spectrum Disorder/genetics  Autistic Disorder  Disease Models, Animal  Dorsal Raphe Nucleus  Genotype  Humans  Male  Mice  Prefrontal Cortex/diagnostic imaging  Reversal Learning  cognitive neuroscience  copy number variation/copy number variants  frontal lobe  genotype-phenotype correlation  imaging genetics  mouse models  serotonin Index. décimale : PER Périodiques Résumé : 2p16.3 deletion, involving NEUREXIN1 (NRXN1) heterozygous deletion, substantially increases the risk of developing autism and other neurodevelopmental disorders. We have a poor understanding of how NRXN1 heterozygosity impacts on brain function and cognition to increase the risk of developing the disorder. Here we characterize the impact of Nrxn1 heterozygosity on cerebral metabolism, in mice, using (14) C-2-deoxyglucose imaging. We also assess performance in an olfactory-based discrimination and reversal learning (OB-DaRL) task and locomotor activity. We use decision tree classifiers to test the predictive relationship between cerebral metabolism and Nrxn1 genotype. Our data show that Nrxn1 heterozygosity induces prefrontal cortex (medial prelimbic cortex, mPrL) hypometabolism and a contrasting dorsal raphé nucleus (DRN) hypermetabolism. Metabolism in these regions allows for the predictive classification of Nrxn1 genotype. Consistent with reduced mPrL glucose utilization, prefrontal cortex insulin receptor signaling is decreased in Nrxn1 (+/-) mice. Behaviorally, Nrxn1 (+/-) mice show enhanced learning of a novel discrimination, impaired reversal learning and an increased latency to make correct choices. In addition, male Nrxn1 (+/-) mice show hyperlocomotor activity. Correlative analysis suggests that mPrL hypometabolism contributes to the enhanced novel odor discrimination seen in Nrxn1 (+/-) mice, while DRN hypermetabolism contributes to their increased latency in making correct choices. The data show that Nrxn1 heterozygosity impacts on prefrontal cortex and serotonin system function, which contribute to the cognitive alterations seen in these animals. The data suggest that Nrxn1 (+/-) mice provide a translational model for the cognitive and behavioral alterations seen in autism and other neurodevelopmental disorders associated with 2p16.3 deletion. LAY SUMMARY: Deletion of the chromosomal region 2p16.3, involving reduced NEUREXIN1 gene expression, dramatically increases the risk of developing autism. Here, we show that reduced Neurexin1 expression, in mice, impacts on the prefrontal cortex and impairs cognitive flexibility. The data suggest that 2p16.3 deletion increases the risk of developing autism by impacting on the prefrontal cortex. Mice with the deletion are a useful model for testing new drugs to treat the cognitive flexibility problems experienced by people with autism. En ligne : https://dx.doi.org/10.1002/aur.2685 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473

Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation / Paola Francesca AJMONE in Journal of Autism and Developmental Disorders, 52-11 (November 2022)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 52-11 (November 2022) . - p.4763-4773 Titre : Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation Type de document : texte imprimé Auteurs : Paola Francesca AJMONE, Auteur ; Beatrice ALLEGRI, Auteur ; Anna CEREDA, Auteur ; Giovanni MICHELINI, Auteur ; Francesca DALL'ARA, Auteur ; Milena MARIANI, Auteur ; Claudia RIGAMONTI, Auteur ; Angelo SELICORNI, Auteur ; Paola VIZZIELLO, Auteur ; Maria Antonella COSTANTINO, Auteur Article en page(s) : p.4763-4773 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/genetics  Cell Cycle Proteins/genetics  De Lange Syndrome/diagnosis  Genotype  Humans  Phenotype  CdLS  Genotype-phenotype correlations  Id  Nipbl  Neuropsychiatric assessment Index. décimale : PER Périodiques Résumé : Behavioural phenotype and autism-related traits of 38 patients affected by Cornelia de Lange syndrome (CdLS) were assessed using a specific neuropsychiatric protocol. Subsequently,we search for possible genotype-phenotype correlations comparing individuals with NIPBL variants and patients with negative molecular results. Firstly results showed a higher percentage of subjects with normal intellectual quotient (IQ) and borderline IQ; adaptive skills were lower than expected for age in all participants. 39.5% of the sample presented with autism spectrum disorder (ASD), NIPBL mutated individuals demonstrated a worse trend in comparison with the clinical diagnosis group. non-truncating individuals displayed no ASD and better communication abilities than truncating individuals. Findings increase our awareness of the strengths and weaknesses points in CdLS individuals. En ligne : http://dx.doi.org/10.1007/s10803-021-05343-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=489 [article] Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation [texte imprimé] / Paola Francesca AJMONE, Auteur ; Beatrice ALLEGRI, Auteur ; Anna CEREDA, Auteur ; Giovanni MICHELINI, Auteur ; Francesca DALL'ARA, Auteur ; Milena MARIANI, Auteur ; Claudia RIGAMONTI, Auteur ; Angelo SELICORNI, Auteur ; Paola VIZZIELLO, Auteur ; Maria Antonella COSTANTINO, Auteur . - p.4763-4773. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 52-11 (November 2022) . - p.4763-4773 Mots-clés : Autism Spectrum Disorder/genetics  Cell Cycle Proteins/genetics  De Lange Syndrome/diagnosis  Genotype  Humans  Phenotype  CdLS  Genotype-phenotype correlations  Id  Nipbl  Neuropsychiatric assessment Index. décimale : PER Périodiques Résumé : Behavioural phenotype and autism-related traits of 38 patients affected by Cornelia de Lange syndrome (CdLS) were assessed using a specific neuropsychiatric protocol. Subsequently,we search for possible genotype-phenotype correlations comparing individuals with NIPBL variants and patients with negative molecular results. Firstly results showed a higher percentage of subjects with normal intellectual quotient (IQ) and borderline IQ; adaptive skills were lower than expected for age in all participants. 39.5% of the sample presented with autism spectrum disorder (ASD), NIPBL mutated individuals demonstrated a worse trend in comparison with the clinical diagnosis group. non-truncating individuals displayed no ASD and better communication abilities than truncating individuals. Findings increase our awareness of the strengths and weaknesses points in CdLS individuals. En ligne : http://dx.doi.org/10.1007/s10803-021-05343-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=489

Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett syndrome / Jenny DOWNS in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett syndrome Type de document : texte imprimé Auteurs : Jenny DOWNS, Auteur ; Kingsley WONG, Auteur ; Helen LEONARD, Auteur Langues : Anglais (eng) Mots-clés : Humans  Rett Syndrome/physiopathology/genetics/complications  Female  Male  Child  Adult  Cross-Sectional Studies  Child, Preschool  Phenotype  Adolescent  Middle Aged  Young Adult  Surveys and Questionnaires  Genotype  Methyl-CpG-Binding Protein 2/genetics  Australia  Sleep Wake Disorders/physiopathology  Behaviour  Outcome measure  Rett syndrome  Taysha  Clinical Trials with Anavex and Newron  All remuneration has been made to  her department. HL: Consultancy for Marinus, Acadia, Avexis and Orion  Clinical  Trials with Anavex and Newron  All remuneration has been made to her department.  KW: Has no competing interests. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Rett syndrome (RTT) is a rare neurodevelopmental disorder with developmental impairments, comorbidities, and abnormal behaviours such as hand stereotypies and emotional features. The Rett Syndrome Behaviour Questionnaire (RSBQ) was developed to describe the behavioural and emotional features of RTT. Little is known how RSBQ scores are associated with genetic and clinical characteristics in RTT. This study investigated relationships between genotype, age, walking, hand function, sleep, and RSBQ total and subscale scores in RTT. METHODS: This is a cross-sectional analysis of data collected in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database. Parent caregivers completed the RSBQ and Sleep Disturbance Scale for Children [subscales for disorders of initiating and maintaining sleep (DIMS), disorders of excessive somnolence (DOES)], and provided information on age, variant type, functional abilities (mobility, hand function), seizure frequency and gastrointestinal problems. Associations between the RSBQ scores and the independent variables were modelled using linear regression. RESULTS: Data were available for 365 individuals with RTT [median (range) age 17.8 (2.9-51.9) years, 2 males]. Compared to adults, 2- to 12-year-old children had higher mean Total, Night-time Behaviour and Fear/Anxiety scores. Compared to individuals with a C-terminal deletion, individuals with the p.Arg255* variant had higher mean Total and Night-time Behaviours scores, whereas the p.Arg294* variant had higher mean Mood scores. Individuals with intermediate mobility and hand function abilities had a higher mean Total score. Total RSBQ and subscale scores were similar across categories for seizures, constipation, and reflux, but were higher with abnormal DIMS and abnormal DOES scores. CONCLUSION: Except for associations with sleep, the RSBQ measures the behavioural phenotype rather than clinical severity in RTT, as traditionally conceptualised in terms of functional abilities and comorbidities. When designing clinical trials, the RSBQ needs to be complemented by other outcome measures to assess specific core functions and associated comorbidities in RTT. En ligne : https://dx.doi.org/10.1186/s11689-024-09575-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett syndrome [texte imprimé] / Jenny DOWNS, Auteur ; Kingsley WONG, Auteur ; Helen LEONARD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Rett Syndrome/physiopathology/genetics/complications  Female  Male  Child  Adult  Cross-Sectional Studies  Child, Preschool  Phenotype  Adolescent  Middle Aged  Young Adult  Surveys and Questionnaires  Genotype  Methyl-CpG-Binding Protein 2/genetics  Australia  Sleep Wake Disorders/physiopathology  Behaviour  Outcome measure  Rett syndrome  Taysha  Clinical Trials with Anavex and Newron  All remuneration has been made to  her department. HL: Consultancy for Marinus, Acadia, Avexis and Orion  Clinical  Trials with Anavex and Newron  All remuneration has been made to her department.  KW: Has no competing interests. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Rett syndrome (RTT) is a rare neurodevelopmental disorder with developmental impairments, comorbidities, and abnormal behaviours such as hand stereotypies and emotional features. The Rett Syndrome Behaviour Questionnaire (RSBQ) was developed to describe the behavioural and emotional features of RTT. Little is known how RSBQ scores are associated with genetic and clinical characteristics in RTT. This study investigated relationships between genotype, age, walking, hand function, sleep, and RSBQ total and subscale scores in RTT. METHODS: This is a cross-sectional analysis of data collected in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database. Parent caregivers completed the RSBQ and Sleep Disturbance Scale for Children [subscales for disorders of initiating and maintaining sleep (DIMS), disorders of excessive somnolence (DOES)], and provided information on age, variant type, functional abilities (mobility, hand function), seizure frequency and gastrointestinal problems. Associations between the RSBQ scores and the independent variables were modelled using linear regression. RESULTS: Data were available for 365 individuals with RTT [median (range) age 17.8 (2.9-51.9) years, 2 males]. Compared to adults, 2- to 12-year-old children had higher mean Total, Night-time Behaviour and Fear/Anxiety scores. Compared to individuals with a C-terminal deletion, individuals with the p.Arg255* variant had higher mean Total and Night-time Behaviours scores, whereas the p.Arg294* variant had higher mean Mood scores. Individuals with intermediate mobility and hand function abilities had a higher mean Total score. Total RSBQ and subscale scores were similar across categories for seizures, constipation, and reflux, but were higher with abnormal DIMS and abnormal DOES scores. CONCLUSION: Except for associations with sleep, the RSBQ measures the behavioural phenotype rather than clinical severity in RTT, as traditionally conceptualised in terms of functional abilities and comorbidities. When designing clinical trials, the RSBQ needs to be complemented by other outcome measures to assess specific core functions and associated comorbidities in RTT. En ligne : https://dx.doi.org/10.1186/s11689-024-09575-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Early social rearing, the V1A arginine vasopressin receptor genotype, and autistic traits in chimpanzees / Alexander WEISS in Autism Research, 14-9 (September 2021)  

Public ISBD [article]  inAutism Research > 14-9 (September 2021) . - p.1843-1853 Titre : Early social rearing, the V1A arginine vasopressin receptor genotype, and autistic traits in chimpanzees Type de document : texte imprimé Auteurs : Alexander WEISS, Auteur ; Vanessa A.D. WILSON, Auteur ; William D. HOPKINS, Auteur Article en page(s) : p.1843-1853 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/genetics  Autistic Disorder/genetics  Genotype  Pan troglodytes/genetics  Receptors, Vasopressin/genetics  Social Behavior  Avpr1a  autism  development  mother  primate  vasopressin Index. décimale : PER Périodiques Résumé : Previous studies found associations between autism-related phenotypes and both rearing and V1A arginine vasopressin receptor (AVPR1A) genotypes. We tested whether these exposures as well as their interaction were associated with autism-related phenotypes in 121 laboratory-housed chimpanzees. We used expert-derived weights to obtain autism scores from ratings on the 43-item Chimpanzee Personality Questionnaire; higher scores indicated more autistic-like traits. The first model included fixed effects for sex, age, and rearing, and a random effect that addressed the relatedness of subjects. The second model was the same except that it also included the rearing × AVPR1A genotype interaction as a fixed effect. Both models indicated that the phenotype was moderately heritable and that chimpanzees reared by their mothers had lower scores on the scale. The effect of genotype in both models indicated that chimpanzees with an indel deletion had higher scores on the scale, although the credible interval included zero. Moreover, the rearing × genotype interaction in the second model indicated that chimpanzees who possessed the non-deletion genotype and who were reared by their mother were at even greater risk. The credible interval for this effect did not include zero, but fit statistics indicated that the model without the interaction was marginally better, and the interaction was in the opposite direction than we expected based on previous work. These findings highlight the importance of rearing effects in the typical social development of our closet-living nonhuman relative. LAY SUMMARY: We tested whether, in chimpanzees, scores on a scale comprising traits that resembled aspects of autism were related to a gene associated with autism in prior research and/or early rearing. Human-reared chimpanzees had higher scores (indicating more autistic-like traits). Chimpanzees that possessed the gene also had higher scores, but we could not exclude the possibility that there was no effect of genotype. These findings suggest that we can measure autism-like characteristics in chimpanzees, and so study it in this species. En ligne : http://dx.doi.org/10.1002/aur.2550 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Early social rearing, the V1A arginine vasopressin receptor genotype, and autistic traits in chimpanzees [texte imprimé] / Alexander WEISS, Auteur ; Vanessa A.D. WILSON, Auteur ; William D. HOPKINS, Auteur . - p.1843-1853. Langues : Anglais (eng) in Autism Research > 14-9 (September 2021) . - p.1843-1853 Mots-clés : Animals  Autism Spectrum Disorder/genetics  Autistic Disorder/genetics  Genotype  Pan troglodytes/genetics  Receptors, Vasopressin/genetics  Social Behavior  Avpr1a  autism  development  mother  primate  vasopressin Index. décimale : PER Périodiques Résumé : Previous studies found associations between autism-related phenotypes and both rearing and V1A arginine vasopressin receptor (AVPR1A) genotypes. We tested whether these exposures as well as their interaction were associated with autism-related phenotypes in 121 laboratory-housed chimpanzees. We used expert-derived weights to obtain autism scores from ratings on the 43-item Chimpanzee Personality Questionnaire; higher scores indicated more autistic-like traits. The first model included fixed effects for sex, age, and rearing, and a random effect that addressed the relatedness of subjects. The second model was the same except that it also included the rearing × AVPR1A genotype interaction as a fixed effect. Both models indicated that the phenotype was moderately heritable and that chimpanzees reared by their mothers had lower scores on the scale. The effect of genotype in both models indicated that chimpanzees with an indel deletion had higher scores on the scale, although the credible interval included zero. Moreover, the rearing × genotype interaction in the second model indicated that chimpanzees who possessed the non-deletion genotype and who were reared by their mother were at even greater risk. The credible interval for this effect did not include zero, but fit statistics indicated that the model without the interaction was marginally better, and the interaction was in the opposite direction than we expected based on previous work. These findings highlight the importance of rearing effects in the typical social development of our closet-living nonhuman relative. LAY SUMMARY: We tested whether, in chimpanzees, scores on a scale comprising traits that resembled aspects of autism were related to a gene associated with autism in prior research and/or early rearing. Human-reared chimpanzees had higher scores (indicating more autistic-like traits). Chimpanzees that possessed the gene also had higher scores, but we could not exclude the possibility that there was no effect of genotype. These findings suggest that we can measure autism-like characteristics in chimpanzees, and so study it in this species. En ligne : http://dx.doi.org/10.1002/aur.2550 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder / Michael YAO in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder Type de document : texte imprimé Auteurs : Michael YAO, Auteur ; Jason DANIELS, Auteur ; Luke GROSVENOR, Auteur ; Valerie MORRILL, Auteur ; Jason I. FEINBERG, Auteur ; Kelly M. BAKULSKI, Auteur ; Joseph PIVEN, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Craig NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Rebecca J. SCHMIDT, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur ; Heather VOLK, Auteur ; Kelly BENKE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Multifactorial Inheritance  Genetic Predisposition to Disease  Male  Female  Genotype  Polymorphism, Single Nucleotide  Autism spectrum disorder (ASD)  Information Loss  Polygenic scores (PGS) Index. décimale : PER Périodiques Résumé : BACKGROUND: Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS. METHODS: We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants. RESULTS: Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric. LIMITATIONS: The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries. CONCLUSIONS: We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits. En ligne : https://dx.doi.org/10.1186/s11689-024-09571-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder [texte imprimé] / Michael YAO, Auteur ; Jason DANIELS, Auteur ; Luke GROSVENOR, Auteur ; Valerie MORRILL, Auteur ; Jason I. FEINBERG, Auteur ; Kelly M. BAKULSKI, Auteur ; Joseph PIVEN, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Craig NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Rebecca J. SCHMIDT, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur ; Heather VOLK, Auteur ; Kelly BENKE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Multifactorial Inheritance  Genetic Predisposition to Disease  Male  Female  Genotype  Polymorphism, Single Nucleotide  Autism spectrum disorder (ASD)  Information Loss  Polygenic scores (PGS) Index. décimale : PER Périodiques Résumé : BACKGROUND: Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS. METHODS: We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants. RESULTS: Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric. LIMITATIONS: The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries. CONCLUSIONS: We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits. En ligne : https://dx.doi.org/10.1186/s11689-024-09571-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Interaction of Blood Manganese Concentrations with GSTT1 in Relation to Autism Spectrum Disorder in Jamaican Children / Mohammad H. RAHBAR in Journal of Autism and Developmental Disorders, 51-6 (June 2021)  

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Research Review: A guide to computing and implementing polygenic scores in developmental research / Andrea G. ALLEGRINI in Journal of Child Psychology and Psychiatry, 63-10 (October 2022)  

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Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study / Jessica MACKAY in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

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Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density / Susan R. BERKOWICZ in Molecular Autism, 7 (2016)  

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Comparative Analysis of Phenotypic and Genotypic Differences Between Individuals Affected by Regressive and Non-Regressive Autism: A Cross-Sectional Study / Alana IABONI ; Brett TROST ; Miriam REUTER ; Zsuzsa LINDENMAIER ; Azadeh KUSHKI ; Elizabeth KELLEY ; Jessica JONES ; Muhammad AYUB ; Stelios GEORGIADES ; Robert NICOLSON ; Elim CHAN ; Andrada CRETU ; Jessica BRIAN ; Evdokia ANAGNOSTOU in Autism Research, 18-6 (June 2025)  

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