7 recherche sur le mot-clé 'Attention Deficit Disorder with Hyperactivity/genetics'

PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder / Jordi PIJUAN in Autism Research, 14-6 (June 2021)  

Public ISBD [article]  inAutism Research > 14-6 (June 2021) . - p.1088-1100 Titre : PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder Type de document : texte imprimé Auteurs : Jordi PIJUAN, Auteur ; Juan Darío ORTIGOZA-ESCOBAR, Auteur ; Juan ORTIZ, Auteur ; Adrián ALCALÁ, Auteur ; María José CALVO, Auteur ; Mariona CUBELLS, Auteur ; Cristina HERNANDO-DAVALILLO, Auteur ; Francesc PALAU, Auteur ; Janet HOENICKA, Auteur Article en page(s) : p.1088-1100 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  DNA Copy Number Variations  Exome  Genetic Predisposition to Disease/genetics  Humans  Nerve Tissue Proteins/genetics  Receptors, Cell Surface  Lrrc40  Plxna2  autism spectrum disorder  diagnosis  neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disability with high heritability yet the genetic etiology remains elusive. Therefore, it is necessary to elucidate new genotype-phenotype relationships for ASD to improve both the etiological knowledge and diagnosis. In this work, a copy-number variant and whole-exome sequencing analysis were performed in an ASD patient with a complex neurobehavioral phenotype with epilepsy and attention deficit hyperactivity disorder. We identified rare recessive single nucleotide variants in the two genes, PLXNA2 encoding Plexin A2 that participates in neurodevelopment, and LRRC40, which encodes Leucine-rich repeat containing protein 40, a protein of unknown function. PLXNA2 showed the heterozygous missense variants c.614G>A (p.Arg205Gln) and c.4904G>A (p.Arg1635Gln) while LRRC40 presented the homozygous missense variant c.1461G>T (p.Leu487Phe). In silico analysis predicted that these variants could be pathogenic. We studied PLXNA2 and LRRC40 mRNA and proteins in fibroblasts from the patient and controls. We observed a significant PlxnA2 subcellular delocalization and very low levels of LRRC40 in the patient. Moreover, we found a novel interaction between PlxnA2 and LRRC40 suggesting that participate in a common neural pathway. This interaction was significant decreased in the patient's fibroblasts. In conclusion, our results identified PLXNA2 and LRRC40 genes as candidates in ASD providing novel clues for the pathogenesis. Further attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD. LAY SUMMARY: Genomics is improving the knowledge and diagnosis of patients with autism spectrum disorder (ASD) yet the genetic etiology remains elusive. Here, using genomic analysis together with experimental functional studies, we identified in an ASD complex patient the PLXNA2 and LRRC40 recessive genes as ASD candidates. Furthermore, we found that the proteins of these genes interact in a common neural network. Therefore, more attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD. En ligne : http://dx.doi.org/10.1002/aur.2502 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder [texte imprimé] / Jordi PIJUAN, Auteur ; Juan Darío ORTIGOZA-ESCOBAR, Auteur ; Juan ORTIZ, Auteur ; Adrián ALCALÁ, Auteur ; María José CALVO, Auteur ; Mariona CUBELLS, Auteur ; Cristina HERNANDO-DAVALILLO, Auteur ; Francesc PALAU, Auteur ; Janet HOENICKA, Auteur . - p.1088-1100. Langues : Anglais (eng) in Autism Research > 14-6 (June 2021) . - p.1088-1100 Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  DNA Copy Number Variations  Exome  Genetic Predisposition to Disease/genetics  Humans  Nerve Tissue Proteins/genetics  Receptors, Cell Surface  Lrrc40  Plxna2  autism spectrum disorder  diagnosis  neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disability with high heritability yet the genetic etiology remains elusive. Therefore, it is necessary to elucidate new genotype-phenotype relationships for ASD to improve both the etiological knowledge and diagnosis. In this work, a copy-number variant and whole-exome sequencing analysis were performed in an ASD patient with a complex neurobehavioral phenotype with epilepsy and attention deficit hyperactivity disorder. We identified rare recessive single nucleotide variants in the two genes, PLXNA2 encoding Plexin A2 that participates in neurodevelopment, and LRRC40, which encodes Leucine-rich repeat containing protein 40, a protein of unknown function. PLXNA2 showed the heterozygous missense variants c.614G>A (p.Arg205Gln) and c.4904G>A (p.Arg1635Gln) while LRRC40 presented the homozygous missense variant c.1461G>T (p.Leu487Phe). In silico analysis predicted that these variants could be pathogenic. We studied PLXNA2 and LRRC40 mRNA and proteins in fibroblasts from the patient and controls. We observed a significant PlxnA2 subcellular delocalization and very low levels of LRRC40 in the patient. Moreover, we found a novel interaction between PlxnA2 and LRRC40 suggesting that participate in a common neural pathway. This interaction was significant decreased in the patient's fibroblasts. In conclusion, our results identified PLXNA2 and LRRC40 genes as candidates in ASD providing novel clues for the pathogenesis. Further attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD. LAY SUMMARY: Genomics is improving the knowledge and diagnosis of patients with autism spectrum disorder (ASD) yet the genetic etiology remains elusive. Here, using genomic analysis together with experimental functional studies, we identified in an ASD complex patient the PLXNA2 and LRRC40 recessive genes as ASD candidates. Furthermore, we found that the proteins of these genes interact in a common neural network. Therefore, more attention to these genes is warranted in genetic studies of patients with neurodevelopmental disorders, particularly ASD. En ligne : http://dx.doi.org/10.1002/aur.2502 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

An atlas of genetic correlations between gestational age and common psychiatric disorders / Yao YAO in Autism Research, 15-6 (June 2022)  

Public ISBD [article]  inAutism Research > 15-6 (June 2022) . - p.1008-1017 Titre : An atlas of genetic correlations between gestational age and common psychiatric disorders Type de document : texte imprimé Auteurs : Yao YAO, Auteur ; Chun'e LI, Auteur ; Peilin MENG, Auteur ; Bolun CHENG, Auteur ; Shiqiang CHENG, Auteur ; Li LIU, Auteur ; Xuena YANG, Auteur ; Yumeng JIA, Auteur ; Yan WEN, Auteur ; Feng ZHANG, Auteur Article en page(s) : p.1008-1017 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  Depressive Disorder, Major/genetics  Female  Genetic Predisposition to Disease  Genome-Wide Association Study  Gestational Age  Humans  Infant, Newborn  Mendelian Randomization Analysis  Premature Birth/genetics  Proteomics  genetic correlation  linkage disequilibrium score regression  psychiatric disorders Index. décimale : PER Périodiques Résumé : We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p?< 0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (r(g) = -0.1405, FDR p = 0.0406), post-term birth and SCZ (r(g) = -0.2003, FDR p = 0.0042). We also observed causal effect of post-term birth on SCZ by MR (P(Weighted median) = 0.037, P(Inverse variance weighted) = 0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2719 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 [article] An atlas of genetic correlations between gestational age and common psychiatric disorders [texte imprimé] / Yao YAO, Auteur ; Chun'e LI, Auteur ; Peilin MENG, Auteur ; Bolun CHENG, Auteur ; Shiqiang CHENG, Auteur ; Li LIU, Auteur ; Xuena YANG, Auteur ; Yumeng JIA, Auteur ; Yan WEN, Auteur ; Feng ZHANG, Auteur . - p.1008-1017. Langues : Anglais (eng) in Autism Research > 15-6 (June 2022) . - p.1008-1017 Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  Depressive Disorder, Major/genetics  Female  Genetic Predisposition to Disease  Genome-Wide Association Study  Gestational Age  Humans  Infant, Newborn  Mendelian Randomization Analysis  Premature Birth/genetics  Proteomics  genetic correlation  linkage disequilibrium score regression  psychiatric disorders Index. décimale : PER Périodiques Résumé : We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p?< 0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (r(g) = -0.1405, FDR p = 0.0406), post-term birth and SCZ (r(g) = -0.2003, FDR p = 0.0042). We also observed causal effect of post-term birth on SCZ by MR (P(Weighted median) = 0.037, P(Inverse variance weighted) = 0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2719 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476

DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders / Michelle T. SIU in Journal of Autism and Developmental Disorders, 51-10 (October 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3610-3623 Titre : DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders Type de document : texte imprimé Auteurs : Michelle T. SIU, Auteur ; Sabrina J. GOODMAN, Auteur ; Isaac YELLAN, Auteur ; Darci T. BUTCHER, Auteur ; Maryam JANGJOO, Auteur ; Daria GRAFODATSKAYA, Auteur ; Rageen RAJENDRAM, Auteur ; Youliang LOU, Auteur ; Rujun ZHANG, Auteur ; Chunhua ZHAO, Auteur ; Robert NICOLSON, Auteur ; Stelios GEORGIADES, Auteur ; Peter SZATMARI, Auteur ; Stephen SCHERER, Auteur ; Wendy ROBERTS, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Rosanna WEKSBERG, Auteur Article en page(s) : p.3610-3623 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  DNA Methylation  Female  Humans  Male  Obsessive-Compulsive Disorder  Oxytocin/metabolism  Receptors, Oxytocin/genetics  Adhd  Asd  Ocd  Oxtr Index. décimale : PER Périodiques Résumé : Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes. En ligne : http://dx.doi.org/10.1007/s10803-020-04792-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453 [article] DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders [texte imprimé] / Michelle T. SIU, Auteur ; Sabrina J. GOODMAN, Auteur ; Isaac YELLAN, Auteur ; Darci T. BUTCHER, Auteur ; Maryam JANGJOO, Auteur ; Daria GRAFODATSKAYA, Auteur ; Rageen RAJENDRAM, Auteur ; Youliang LOU, Auteur ; Rujun ZHANG, Auteur ; Chunhua ZHAO, Auteur ; Robert NICOLSON, Auteur ; Stelios GEORGIADES, Auteur ; Peter SZATMARI, Auteur ; Stephen SCHERER, Auteur ; Wendy ROBERTS, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Rosanna WEKSBERG, Auteur . - p.3610-3623. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3610-3623 Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  Autism Spectrum Disorder/genetics  DNA Methylation  Female  Humans  Male  Obsessive-Compulsive Disorder  Oxytocin/metabolism  Receptors, Oxytocin/genetics  Adhd  Asd  Ocd  Oxtr Index. décimale : PER Périodiques Résumé : Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes. En ligne : http://dx.doi.org/10.1007/s10803-020-04792-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453

Characterizing genetic pathways unique to autism spectrum disorder at multiple levels of biological analysis / Lukas S. SCHAFFER in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 46p. Titre : Characterizing genetic pathways unique to autism spectrum disorder at multiple levels of biological analysis Type de document : texte imprimé Auteurs : Lukas S. SCHAFFER, Auteur ; Sophie BREUNIG, Auteur ; Jeremy M. LAWRENCE, Auteur ; Isabelle F FOOTE, Auteur ; Andrew D. GROTZINGER, Auteur Article en page(s) : 46p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Genetic Predisposition to Disease  Attention Deficit Disorder with Hyperactivity/genetics  Phenotype  Transcriptome  Male  Female  Child  Polymorphism, Single Nucleotide  Latent Class Analysis  Attention-deficit/hyperactivity disorder  Autism spectrum disorder  Comorbidity  Genomic SEM  Multivariate genomics  Neurodevelopmental disorders  Psychiatric genetics Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical patterns of social functioning and repetitive/restricted behaviors. ASD commonly co-occurs with ADHD and, despite their clinical distinctiveness, the two share considerable genetic overlap. Given their shared genetic liability, it is unclear which genetic pathways increase the likelihood of ASD independently of ADHD. METHODS: We applied Genomic Structural Equation Modeling (SEM) to GWAS summary statistics for ASD and childhood-diagnosed ADHD, decomposing the genetic variance for ASD into that which is unique to ASD (uASD) and that which is shared with ADHD. We computed genetic correlations between uASD and 83 external traits to estimate genetic overlap between uASD and other clinically relevant phenotypes. We went on to apply Stratified Genomic SEM to identify classes of genes enriched for uASD. Finally, we implemented Transcriptome-Wide SEM (T-SEM) to explore patterns of gene-expression associated with uASD. RESULTS: We observed positive genetic correlations between uASD and several external traits, most notably those relating to cognitive/educational outcomes and internalizing psychiatric traits. Stratified Genomic SEM showed that heritability for uASD was significantly enriched in genes involved in evolutionarily conserved processes, as well as for a histone mark in the germinal matrix. T-SEM revealed 83 unique genes with expression associated with uASD, 34 of which were novel with respect to univariate analyses. These genes were overrepresented in skin-related pathologies. LIMITATIONS: Our study was limited by summary statistics derived exclusively from individuals of European ancestry. Additionally, using data based on a general ASD diagnosis limits our ability to understand genetic factors contributing to the pronounced clinical heterogeneity in ASD. CONCLUSIONS: Our findings delineate the unique genetic underpinnings of ASD that are independent of ADHD at the genome-wide, functional, and gene expression level of analysis. In addition, we identify novel associations previously masked by their diametric effects on ADHD. Collectively, these results provide insight into the processes that make ASD biologically unique. En ligne : https://dx.doi.org/10.1186/s13229-024-00624-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Characterizing genetic pathways unique to autism spectrum disorder at multiple levels of biological analysis [texte imprimé] / Lukas S. SCHAFFER, Auteur ; Sophie BREUNIG, Auteur ; Jeremy M. LAWRENCE, Auteur ; Isabelle F FOOTE, Auteur ; Andrew D. GROTZINGER, Auteur . - 46p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 46p. Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Genetic Predisposition to Disease  Attention Deficit Disorder with Hyperactivity/genetics  Phenotype  Transcriptome  Male  Female  Child  Polymorphism, Single Nucleotide  Latent Class Analysis  Attention-deficit/hyperactivity disorder  Autism spectrum disorder  Comorbidity  Genomic SEM  Multivariate genomics  Neurodevelopmental disorders  Psychiatric genetics Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical patterns of social functioning and repetitive/restricted behaviors. ASD commonly co-occurs with ADHD and, despite their clinical distinctiveness, the two share considerable genetic overlap. Given their shared genetic liability, it is unclear which genetic pathways increase the likelihood of ASD independently of ADHD. METHODS: We applied Genomic Structural Equation Modeling (SEM) to GWAS summary statistics for ASD and childhood-diagnosed ADHD, decomposing the genetic variance for ASD into that which is unique to ASD (uASD) and that which is shared with ADHD. We computed genetic correlations between uASD and 83 external traits to estimate genetic overlap between uASD and other clinically relevant phenotypes. We went on to apply Stratified Genomic SEM to identify classes of genes enriched for uASD. Finally, we implemented Transcriptome-Wide SEM (T-SEM) to explore patterns of gene-expression associated with uASD. RESULTS: We observed positive genetic correlations between uASD and several external traits, most notably those relating to cognitive/educational outcomes and internalizing psychiatric traits. Stratified Genomic SEM showed that heritability for uASD was significantly enriched in genes involved in evolutionarily conserved processes, as well as for a histone mark in the germinal matrix. T-SEM revealed 83 unique genes with expression associated with uASD, 34 of which were novel with respect to univariate analyses. These genes were overrepresented in skin-related pathologies. LIMITATIONS: Our study was limited by summary statistics derived exclusively from individuals of European ancestry. Additionally, using data based on a general ASD diagnosis limits our ability to understand genetic factors contributing to the pronounced clinical heterogeneity in ASD. CONCLUSIONS: Our findings delineate the unique genetic underpinnings of ASD that are independent of ADHD at the genome-wide, functional, and gene expression level of analysis. In addition, we identify novel associations previously masked by their diametric effects on ADHD. Collectively, these results provide insight into the processes that make ASD biologically unique. En ligne : https://dx.doi.org/10.1186/s13229-024-00624-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538