Family-based association testing of OCD-associated SNPs of SLC1A1 in an autism sample / Camille W. BRUNE in Autism Research, 1-2 (April 2008)  

Public ISBD [article]  inAutism Research > 1-2 (April 2008) . - p.108-113 Titre : Family-based association testing of OCD-associated SNPs of SLC1A1 in an autism sample Type de document : texte imprimé Auteurs : Camille W. BRUNE, Auteur ; Catherine LORD, Auteur ; Gregory L. HANNA, Auteur ; Eric COURCHESNE, Auteur ; Edwin H. Jr COOK, Auteur ; Bennett L. LEVENTHAL, Auteur ; Soo-Jeong KIM, Auteur Année de publication : 2008 Article en page(s) : p.108-113 Langues : Anglais (eng) Mots-clés : autism SLC1A1 OCD association Index. décimale : PER Périodiques Résumé : Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. En ligne : http://dx.doi.org/10.1002/aur.11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=930 [article] Family-based association testing of OCD-associated SNPs of SLC1A1 in an autism sample [texte imprimé] / Camille W. BRUNE, Auteur ; Catherine LORD, Auteur ; Gregory L. HANNA, Auteur ; Eric COURCHESNE, Auteur ; Edwin H. Jr COOK, Auteur ; Bennett L. LEVENTHAL, Auteur ; Soo-Jeong KIM, Auteur . - 2008 . - p.108-113. Langues : Anglais (eng) in Autism Research > 1-2 (April 2008) . - p.108-113 Mots-clés : autism SLC1A1 OCD association Index. décimale : PER Périodiques Résumé : Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons. En ligne : http://dx.doi.org/10.1002/aur.11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=930

Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation / Sarah J. GOODMAN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation Type de document : texte imprimé Auteurs : Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation [texte imprimé] / Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

The Obsessive Compulsive Scale of the Child Behavior Checklist predicts obsessive-compulsive disorder: a receiver operating characteristic curve analysis / James J. HUDZIAK in Journal of Child Psychology and Psychiatry, 47-2 (February 2006)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 47-2 (February 2006) . - p.160–166 Titre : The Obsessive Compulsive Scale of the Child Behavior Checklist predicts obsessive-compulsive disorder: a receiver operating characteristic curve analysis Type de document : texte imprimé Auteurs : James J. HUDZIAK, Auteur ; Robert R. ALTHOFF, Auteur ; Catherine STANGER, Auteur ; Catarina E.M. VAN BEIJSTERVELDT, Auteur ; Elliot C. NELSON, Auteur ; Gregory L. HANNA, Auteur ; Dorret I. BOOMSMA, Auteur ; Richard D. TODD, Auteur Année de publication : 2006 Article en page(s) : p.160–166 Langues : Anglais (eng) Mots-clés : Obsessive-compulsive-disorder Child-Behavior-Checklist prevalence Obsessive-Compulsive-Scale Index. décimale : PER Périodiques Résumé : Background: The purpose of this study was to determine a score on the Obsessive Compulsive Scale (OCS) from the Child Behavior Checklist (CBCL) to screen for obsessive compulsive disorder (OCD) in children and to rigorously test the specificity and sensitivity of a single cutpoint. Methods: A receiver operating characteristic (ROC) curve analysis was applied to data from 61 patients with clinically determined OCD, 64 clinical controls and 73 general population controls to determine the best sum score on the CBCL-OCS to predict confirmed OCD in children. Using the ROC-determined cutoff, this score was applied to a national sample of CBCL data from 2460 singleton children ages 4–18 and to 20,016 children ages 7–18 from three large general population twin samples to determine the estimated prevalence in the general population. Results: Using a CBCL-OCS score of 5 demonstrated an area under the curve (AUC) of .88 with high sensitivity (92%) and moderate specificity (67%) compared to clinical controls. Compared to the general population controls, the AUC was .96 with high sensitivity (92%) and specificity (89%). In the twin samples, the number of participants with CBCL-OCS scores above this cutpoint was 2.3–7.1%. Conclusions: These findings suggest that the OCS of the CBCL may provide a highly effective way to screen for childhood OCD, and that the prevalence of childhood OCD may have been underestimated, thus prompting the need for further research into screening children for this condition. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2005.01465.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=714 [article] The Obsessive Compulsive Scale of the Child Behavior Checklist predicts obsessive-compulsive disorder: a receiver operating characteristic curve analysis [texte imprimé] / James J. HUDZIAK, Auteur ; Robert R. ALTHOFF, Auteur ; Catherine STANGER, Auteur ; Catarina E.M. VAN BEIJSTERVELDT, Auteur ; Elliot C. NELSON, Auteur ; Gregory L. HANNA, Auteur ; Dorret I. BOOMSMA, Auteur ; Richard D. TODD, Auteur . - 2006 . - p.160–166. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 47-2 (February 2006) . - p.160–166 Mots-clés : Obsessive-compulsive-disorder Child-Behavior-Checklist prevalence Obsessive-Compulsive-Scale Index. décimale : PER Périodiques Résumé : Background: The purpose of this study was to determine a score on the Obsessive Compulsive Scale (OCS) from the Child Behavior Checklist (CBCL) to screen for obsessive compulsive disorder (OCD) in children and to rigorously test the specificity and sensitivity of a single cutpoint. Methods: A receiver operating characteristic (ROC) curve analysis was applied to data from 61 patients with clinically determined OCD, 64 clinical controls and 73 general population controls to determine the best sum score on the CBCL-OCS to predict confirmed OCD in children. Using the ROC-determined cutoff, this score was applied to a national sample of CBCL data from 2460 singleton children ages 4–18 and to 20,016 children ages 7–18 from three large general population twin samples to determine the estimated prevalence in the general population. Results: Using a CBCL-OCS score of 5 demonstrated an area under the curve (AUC) of .88 with high sensitivity (92%) and moderate specificity (67%) compared to clinical controls. Compared to the general population controls, the AUC was .96 with high sensitivity (92%) and specificity (89%). In the twin samples, the number of participants with CBCL-OCS scores above this cutpoint was 2.3–7.1%. Conclusions: These findings suggest that the OCS of the CBCL may provide a highly effective way to screen for childhood OCD, and that the prevalence of childhood OCD may have been underestimated, thus prompting the need for further research into screening children for this condition. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2005.01465.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=714

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation / MatthewJ GAZZELLONE in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.36 Titre : Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation Type de document : texte imprimé Auteurs : MatthewJ GAZZELLONE, Auteur ; Mehdi ZARREI, Auteur ; Christie L. BURTON, Auteur ; Susan WALKER, Auteur ; Mohammed UDDIN, Auteur ; S.M. SHAHEEN, Auteur ; Julie COSTE, Auteur ; Rageen RAJENDRAM, Auteur ; Reva J. SCHACHTER, Auteur ; Marlena COLASANTO, Auteur ; Gregory L. HANNA, Auteur ; David R. ROSENBERG, Auteur ; Noam SORENI, Auteur ; Kate D. FITZGERALD, Auteur ; Christian R. MARSHALL, Auteur ; Janet A. BUCHANAN, Auteur ; Daniele MERICO, Auteur ; Paul 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 [article] Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation [texte imprimé] / MatthewJ GAZZELLONE, Auteur ; Mehdi ZARREI, Auteur ; Christie L. BURTON, Auteur ; Susan WALKER, Auteur ; Mohammed UDDIN, Auteur ; S.M. SHAHEEN, Auteur ; Julie COSTE, Auteur ; Rageen RAJENDRAM, Auteur ; Reva J. SCHACHTER, Auteur ; Marlena COLASANTO, Auteur ; Gregory L. HANNA, Auteur ; David R. ROSENBERG, Auteur ; Noam SORENI, Auteur ; Kate D. FITZGERALD, Auteur ; Christian R. MARSHALL, Auteur ; Janet A. BUCHANAN, Auteur ; Daniele MERICO, Auteur ; Paul 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

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