Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders / K. LI in Journal of Autism and Developmental Disorders, 52-3 (March 2022)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 52-3 (March 2022) . - p.1299-1313 Titre : Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders Type de document : Texte imprimé et/ou numérique Auteurs : K. LI, Auteur ; Z. FANG, Auteur ; G. ZHAO, Auteur ; B. LI, Auteur ; C. CHEN, Auteur ; L. XIA, Auteur ; L. WANG, Auteur ; T. LUO, Auteur ; X. WANG, Auteur ; Z. WANG, Auteur ; Y. ZHANG, Auteur ; Y. JIANG, Auteur ; Q. PAN, Auteur ; Z. HU, Auteur ; H. GUO, Auteur ; B. TANG, Auteur ; C. LIU, Auteur ; Z. SUN, Auteur ; K. XIA, Auteur ; J. LI, Auteur Article en page(s) : p.1299-1313 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/genetics  Genetic Predisposition to Disease  Humans  Intellectual Disability/genetics  Mutation  Phenotype  Schizophrenia  Candidate gene  De novo mutation  Expression pattern  Functional network  Neuropsychiatric disorder Index. décimale : PER Périodiques Résumé : The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR? En ligne : http://dx.doi.org/10.1007/s10803-021-05031-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455 [article] Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders [Texte imprimé et/ou numérique] / K. LI, Auteur ; Z. FANG, Auteur ; G. ZHAO, Auteur ; B. LI, Auteur ; C. CHEN, Auteur ; L. XIA, Auteur ; L. WANG, Auteur ; T. LUO, Auteur ; X. WANG, Auteur ; Z. WANG, Auteur ; Y. ZHANG, Auteur ; Y. JIANG, Auteur ; Q. PAN, Auteur ; Z. HU, Auteur ; H. GUO, Auteur ; B. TANG, Auteur ; C. LIU, Auteur ; Z. SUN, Auteur ; K. XIA, Auteur ; J. LI, Auteur . - p.1299-1313. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 52-3 (March 2022) . - p.1299-1313 Mots-clés : Autism Spectrum Disorder/genetics  Genetic Predisposition to Disease  Humans  Intellectual Disability/genetics  Mutation  Phenotype  Schizophrenia  Candidate gene  De novo mutation  Expression pattern  Functional network  Neuropsychiatric disorder Index. décimale : PER Périodiques Résumé : The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR? En ligne : http://dx.doi.org/10.1007/s10803-021-05031-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455

Emotional functioning and the development of internalizing and externalizing problems in young boys with and without autism spectrum disorder / B. LI in Autism, 24-1 (January 2020)  

Public ISBD [article]  inAutism > 24-1 (January 2020) . - p.200-210 Titre : Emotional functioning and the development of internalizing and externalizing problems in young boys with and without autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : B. LI, Auteur ; Marieke G. N. BOS, Auteur ; L. STOCKMANN, Auteur ; C. RIEFFE, Auteur Article en page(s) : p.200-210 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  comorbid psychopathology  emotion control  emotion recognition  emotion vocabulary  longitudinal study  preschool Index. décimale : PER Périodiques Résumé : Children with autism spectrum disorder are at risk of developing internalizing and externalizing problems. However, information on early development of behavior problems and the contributing role of emotional functioning in preschool children with autism spectrum disorder is scarce. This study collected data of boys with and without autism spectrum disorder (N = 156; age: 2-6 years) over three consecutive years (three waves), about their internalizing and externalizing symptoms and emotional functioning (i.e. emotion control, recognition, and vocabulary), using parent-report questionnaires. No age effect was found on internalizing or externalizing problems for boys with and without autism spectrum disorder. Boys with autism spectrum disorder displayed more behavior problems than their typically developing peers and showed lower levels of emotional functioning. Better emotion control and improved emotion recognition were associated with a decrease in problem behaviors for boys with and without autism spectrum disorder, whereas improved emotion vocabulary was uniquely related to a decrease in externalizing problems in boys with autism spectrum disorder. Our findings suggest that boys with and without autism spectrum disorder showed similar developmental courses of internalizing and externalizing problems. However, lower levels of emotional functioning were already more pronounced in boys with autism spectrum disorder at a young age. This contributes to higher levels of behavior problems. En ligne : http://dx.doi.org/10.1177/1362361319874644 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Emotional functioning and the development of internalizing and externalizing problems in young boys with and without autism spectrum disorder [Texte imprimé et/ou numérique] / B. LI, Auteur ; Marieke G. N. BOS, Auteur ; L. STOCKMANN, Auteur ; C. RIEFFE, Auteur . - p.200-210. Langues : Anglais (eng) in Autism > 24-1 (January 2020) . - p.200-210 Mots-clés : autism spectrum disorder  comorbid psychopathology  emotion control  emotion recognition  emotion vocabulary  longitudinal study  preschool Index. décimale : PER Périodiques Résumé : Children with autism spectrum disorder are at risk of developing internalizing and externalizing problems. However, information on early development of behavior problems and the contributing role of emotional functioning in preschool children with autism spectrum disorder is scarce. This study collected data of boys with and without autism spectrum disorder (N = 156; age: 2-6 years) over three consecutive years (three waves), about their internalizing and externalizing symptoms and emotional functioning (i.e. emotion control, recognition, and vocabulary), using parent-report questionnaires. No age effect was found on internalizing or externalizing problems for boys with and without autism spectrum disorder. Boys with autism spectrum disorder displayed more behavior problems than their typically developing peers and showed lower levels of emotional functioning. Better emotion control and improved emotion recognition were associated with a decrease in problem behaviors for boys with and without autism spectrum disorder, whereas improved emotion vocabulary was uniquely related to a decrease in externalizing problems in boys with autism spectrum disorder. Our findings suggest that boys with and without autism spectrum disorder showed similar developmental courses of internalizing and externalizing problems. However, lower levels of emotional functioning were already more pronounced in boys with autism spectrum disorder at a young age. This contributes to higher levels of behavior problems. En ligne : http://dx.doi.org/10.1177/1362361319874644 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism / R. CHEN in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 14p. Titre : Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism Type de document : Texte imprimé et/ou numérique Auteurs : R. CHEN, Auteur ; L. K. DAVIS, Auteur ; S. GUTER, Auteur ; Q. WEI, Auteur ; S. JACOB, Auteur ; M. H. POTTER, Auteur ; Nancy J. COX, Auteur ; Edwin H. Jr COOK, Auteur ; J. S. SUTCLIFFE, Auteur ; B. LI, Auteur Article en page(s) : 14p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/*genetics/metabolism  Endophenotypes/blood  Exome  Female  Forkhead Transcription Factors/*genetics  Genetic Predisposition to Disease  Humans  Jumonji Domain-Containing Histone Demethylases/*genetics  Male  *Mutation  Nuclear Proteins/*genetics  Repressor Proteins/*genetics  Sequence Analysis, DNA/methods  Serotonin/*blood  Signal Transduction  Ubiquitin-Specific Proteases/*genetics  *5-ht  *Autism  *Autism spectrum disorder  *Compound heterozygotes  *De novo mutation  *Endophenotype  *Group-wise transmission/disequilibrium test  *Hyperserotonemia  *Rare variants  *Serotonin  *Whole exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown. METHODS: In this study, pursuing the hypothesis that de novo variants (DNVs) and rare risk alleles acting in a recessive mode may play an important role in predisposition of hyperserotonemia in people with ASD, we carried out whole exome sequencing (WES) in 116 ASD parent-proband trios with most (107) probands having 5-HT measurements. RESULTS: Combined with published ASD DNVs, we identified USP15 as having recurrent de novo loss of function mutations and discovered evidence supporting two other known genes with recurrent DNVs (FOXP1 and KDM5B). Genes harboring functional DNVs significantly overlap with functional/disease gene sets known to be involved in ASD etiology, including FMRP targets and synaptic formation and transcriptional regulation genes. We grouped the probands into High-5HT and Normal-5HT groups based on normalized serotonin levels, and used network-based gene set enrichment analysis (NGSEA) to identify novel hyperserotonemia-related ASD genes based on LoF and missense DNVs. We found enrichment in the High-5HT group for a gene network module (DAWN-1) previously implicated in ASD, and this points to the TGF-beta pathway and cell junction processes. Through analysis of rare recessively acting variants (RAVs), we also found that rare compound heterozygotes (CHs) in the High-5HT group were enriched for loci in an ASD-associated gene set. Finally, we carried out rare variant group-wise transmission disequilibrium tests (gTDT) and observed significant association of rare variants in genes encoding a subset of the serotonin pathway with ASD. CONCLUSIONS: Our study identified USP15 as a novel gene implicated in ASD based on recurrent DNVs. It also demonstrates the potential value of 5-HT as an effective endophenotype for gene discovery in ASD, and the effectiveness of this strategy needs to be further explored in studies of larger sample sizes. En ligne : http://dx.doi.org/10.1186/s13229-017-0130-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism [Texte imprimé et/ou numérique] / R. CHEN, Auteur ; L. K. DAVIS, Auteur ; S. GUTER, Auteur ; Q. WEI, Auteur ; S. JACOB, Auteur ; M. H. POTTER, Auteur ; Nancy J. COX, Auteur ; Edwin H. Jr COOK, Auteur ; J. S. SUTCLIFFE, Auteur ; B. LI, Auteur . - 14p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 14p. Mots-clés : Autism Spectrum Disorder/*genetics/metabolism  Endophenotypes/blood  Exome  Female  Forkhead Transcription Factors/*genetics  Genetic Predisposition to Disease  Humans  Jumonji Domain-Containing Histone Demethylases/*genetics  Male  *Mutation  Nuclear Proteins/*genetics  Repressor Proteins/*genetics  Sequence Analysis, DNA/methods  Serotonin/*blood  Signal Transduction  Ubiquitin-Specific Proteases/*genetics  *5-ht  *Autism  *Autism spectrum disorder  *Compound heterozygotes  *De novo mutation  *Endophenotype  *Group-wise transmission/disequilibrium test  *Hyperserotonemia  *Rare variants  *Serotonin  *Whole exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown. METHODS: In this study, pursuing the hypothesis that de novo variants (DNVs) and rare risk alleles acting in a recessive mode may play an important role in predisposition of hyperserotonemia in people with ASD, we carried out whole exome sequencing (WES) in 116 ASD parent-proband trios with most (107) probands having 5-HT measurements. RESULTS: Combined with published ASD DNVs, we identified USP15 as having recurrent de novo loss of function mutations and discovered evidence supporting two other known genes with recurrent DNVs (FOXP1 and KDM5B). Genes harboring functional DNVs significantly overlap with functional/disease gene sets known to be involved in ASD etiology, including FMRP targets and synaptic formation and transcriptional regulation genes. We grouped the probands into High-5HT and Normal-5HT groups based on normalized serotonin levels, and used network-based gene set enrichment analysis (NGSEA) to identify novel hyperserotonemia-related ASD genes based on LoF and missense DNVs. We found enrichment in the High-5HT group for a gene network module (DAWN-1) previously implicated in ASD, and this points to the TGF-beta pathway and cell junction processes. Through analysis of rare recessively acting variants (RAVs), we also found that rare compound heterozygotes (CHs) in the High-5HT group were enriched for loci in an ASD-associated gene set. Finally, we carried out rare variant group-wise transmission disequilibrium tests (gTDT) and observed significant association of rare variants in genes encoding a subset of the serotonin pathway with ASD. CONCLUSIONS: Our study identified USP15 as a novel gene implicated in ASD based on recurrent DNVs. It also demonstrates the potential value of 5-HT as an effective endophenotype for gene discovery in ASD, and the effectiveness of this strategy needs to be further explored in studies of larger sample sizes. En ligne : http://dx.doi.org/10.1186/s13229-017-0130-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

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