2 recherche sur le mot-clé 'Snp'

Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity—implications for autism / Madhabi BARUA in Autism Research, 4-4 (August 2011)  

Public ISBD [article]  inAutism Research > 4-4 (August 2011) . - p.262-270 Titre : Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity—implications for autism Type de document : Texte imprimé et/ou numérique Auteurs : Madhabi BARUA, Auteur ; Edmund C. JENKINS, Auteur ; Wenqiang CHEN, Auteur ; Salomon KUIZON, Auteur ; Raju K. PULLARKAT, Auteur ; Mohammed A. JUNAID, Auteur Année de publication : 2011 Article en page(s) : p.262-270 Langues : Anglais (eng) Mots-clés : autism  glyoxalase I  SNP  advanced glycation endproducts (AGEs)  receptor for advanced glycation end products (RAGEs)  methylglyoxal Index. décimale : PER Périodiques Résumé : Autism is a pervasive, heterogeneous, neurodevelopmental disability characterized by impairments in verbal communications, reciprocal social interactions, and restricted repetitive stereotyped behaviors. Evidence suggests the involvement of multiple genetic factors in the etiology of autism, and extensive genome-wide association studies have revealed several candidate genes that bear single nucleotide polymorphisms (SNPs) in non-coding and coding regions. We have shown that a non-conservative, non-synonymous SNP in the glyoxalase I gene, GLOI, may be an autism susceptibility factor. The GLOI rs2736654 SNP is a C→A change that causes an Ala111Glu change in the Glo1 enzyme. To identify the significance of the SNP, we have conducted functional assays for Glo1. We now present evidence that the presence of the A-allele at rs2736654 results in reduced enzyme activity. Glo1 activity is decreased in lymphoblastoid cells that are homozygous for the A allele. The Glu-isoform of Glo1 in these cells is hyperphosphorylated. Direct HPLC measurements of the glyoxalase I substrate, methylglyoxal (MG), show an increase in MG in these cells. Western blot analysis revealed elevated levels of the receptor for advanced glycation end products (RAGEs). We also show that MG is toxic to the developing neuronal cells. We suggest that accumulation of MG results in the formation of AGEs, which induce expression of the RAGE that during crucial neuronal development may be a factor in the pathology of autism. En ligne : http://dx.doi.org/10.1002/aur.197 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=141 [article] Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity—implications for autism [Texte imprimé et/ou numérique] / Madhabi BARUA, Auteur ; Edmund C. JENKINS, Auteur ; Wenqiang CHEN, Auteur ; Salomon KUIZON, Auteur ; Raju K. PULLARKAT, Auteur ; Mohammed A. JUNAID, Auteur . - 2011 . - p.262-270. Langues : Anglais (eng) in Autism Research > 4-4 (August 2011) . - p.262-270 Mots-clés : autism  glyoxalase I  SNP  advanced glycation endproducts (AGEs)  receptor for advanced glycation end products (RAGEs)  methylglyoxal Index. décimale : PER Périodiques Résumé : Autism is a pervasive, heterogeneous, neurodevelopmental disability characterized by impairments in verbal communications, reciprocal social interactions, and restricted repetitive stereotyped behaviors. Evidence suggests the involvement of multiple genetic factors in the etiology of autism, and extensive genome-wide association studies have revealed several candidate genes that bear single nucleotide polymorphisms (SNPs) in non-coding and coding regions. We have shown that a non-conservative, non-synonymous SNP in the glyoxalase I gene, GLOI, may be an autism susceptibility factor. The GLOI rs2736654 SNP is a C→A change that causes an Ala111Glu change in the Glo1 enzyme. To identify the significance of the SNP, we have conducted functional assays for Glo1. We now present evidence that the presence of the A-allele at rs2736654 results in reduced enzyme activity. Glo1 activity is decreased in lymphoblastoid cells that are homozygous for the A allele. The Glu-isoform of Glo1 in these cells is hyperphosphorylated. Direct HPLC measurements of the glyoxalase I substrate, methylglyoxal (MG), show an increase in MG in these cells. Western blot analysis revealed elevated levels of the receptor for advanced glycation end products (RAGEs). We also show that MG is toxic to the developing neuronal cells. We suggest that accumulation of MG results in the formation of AGEs, which induce expression of the RAGE that during crucial neuronal development may be a factor in the pathology of autism. En ligne : http://dx.doi.org/10.1002/aur.197 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=141

Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder / H. PEYRE in Journal of Child Psychology and Psychiatry, 62-11 (November 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1285-1296 Titre : Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder Type de document : Texte imprimé et/ou numérique Auteurs : H. PEYRE, Auteur ; T. SCHOELER, Auteur ; C. LIU, Auteur ; C. M. WILLIAMS, Auteur ; N. HOERTEL, Auteur ; A. HAVDAHL, Auteur ; J. B. PINGAULT, Auteur Article en page(s) : p.1285-1296 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/epidemiology/genetics  Autism Spectrum Disorder/epidemiology/genetics  Comorbidity  Genome-Wide Association Study  Genomics  Humans  Paired Box Transcription Factors/genetics  Polymorphism, Single Nucleotide  Repressor Proteins/genetics  Autism spectrum disorder  Gwas  Snp  attention deficit hyperactivity disorder  colocalization  common genetic variants  comorbidity  genomic structural equation modelling Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two highly heritable neurodevelopmental disorders. Several lines of evidence point towards the presence of shared genetic factors underlying ASD and ADHD. We conducted genomic analyses of common risk variants (i.e. single nucleotide polymorphisms, SNPs) shared by ASD and ADHD, and those specific to each disorder. METHODS: With the summary data from two GWAS, one on ASD (N = 46,350) and another on ADHD (N = 55,374) individuals, we used genomic structural equation modelling and colocalization analysis to identify SNPs shared by ASD and ADHD and SNPs specific to each disorder. Functional genomic analyses were then conducted on shared and specific common genetic variants. Finally, we performed a bidirectional Mendelian randomization analysis to test whether the shared genetic risk between ASD and ADHD was interpretable in terms of reciprocal relationships between ASD and ADHD. RESULTS: We found that 37.5% of the SNPs associated with ASD (at p < 1e-6) colocalized with ADHD SNPs and that 19.6% of the SNPs associated with ADHD colocalized with ASD SNPs. We identified genes mapped to SNPs that are specific to ASD or ADHD and that are shared by ASD and ADHD, including two novel genes INSM1 and PAX1. Our bidirectional Mendelian randomization analyses indicated that the risk of ASD was associated with an increased risk of ADHD and vice versa. CONCLUSIONS: Using multivariate genomic analyses, the present study uncovers shared and specific genetic variants associated with ASD and ADHD. Further functional investigation of genes mapped to those shared variants may help identify pathophysiological pathways and new targets for treatment. En ligne : http://dx.doi.org/10.1111/jcpp.13479 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] Combining multivariate genomic approaches to elucidate the comorbidity between autism spectrum disorder and attention deficit hyperactivity disorder [Texte imprimé et/ou numérique] / H. PEYRE, Auteur ; T. SCHOELER, Auteur ; C. LIU, Auteur ; C. M. WILLIAMS, Auteur ; N. HOERTEL, Auteur ; A. HAVDAHL, Auteur ; J. B. PINGAULT, Auteur . - p.1285-1296. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-11 (November 2021) . - p.1285-1296 Mots-clés : Attention Deficit Disorder with Hyperactivity/epidemiology/genetics  Autism Spectrum Disorder/epidemiology/genetics  Comorbidity  Genome-Wide Association Study  Genomics  Humans  Paired Box Transcription Factors/genetics  Polymorphism, Single Nucleotide  Repressor Proteins/genetics  Autism spectrum disorder  Gwas  Snp  attention deficit hyperactivity disorder  colocalization  common genetic variants  comorbidity  genomic structural equation modelling Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two highly heritable neurodevelopmental disorders. Several lines of evidence point towards the presence of shared genetic factors underlying ASD and ADHD. We conducted genomic analyses of common risk variants (i.e. single nucleotide polymorphisms, SNPs) shared by ASD and ADHD, and those specific to each disorder. METHODS: With the summary data from two GWAS, one on ASD (N = 46,350) and another on ADHD (N = 55,374) individuals, we used genomic structural equation modelling and colocalization analysis to identify SNPs shared by ASD and ADHD and SNPs specific to each disorder. Functional genomic analyses were then conducted on shared and specific common genetic variants. Finally, we performed a bidirectional Mendelian randomization analysis to test whether the shared genetic risk between ASD and ADHD was interpretable in terms of reciprocal relationships between ASD and ADHD. RESULTS: We found that 37.5% of the SNPs associated with ASD (at p < 1e-6) colocalized with ADHD SNPs and that 19.6% of the SNPs associated with ADHD colocalized with ASD SNPs. We identified genes mapped to SNPs that are specific to ASD or ADHD and that are shared by ASD and ADHD, including two novel genes INSM1 and PAX1. Our bidirectional Mendelian randomization analyses indicated that the risk of ASD was associated with an increased risk of ADHD and vice versa. CONCLUSIONS: Using multivariate genomic analyses, the present study uncovers shared and specific genetic variants associated with ASD and ADHD. Further functional investigation of genes mapped to those shared variants may help identify pathophysiological pathways and new targets for treatment. En ligne : http://dx.doi.org/10.1111/jcpp.13479 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456