Lack of replication of previous autism spectrum disorder GWAS hits in European populations / Bàrbara TORRICO in Autism Research, 10-2 (February 2017)  

Public ISBD [article]  inAutism Research > 10-2 (February 2017) . - p.202-211 Titre : Lack of replication of previous autism spectrum disorder GWAS hits in European populations Type de document : Texte imprimé et/ou numérique Auteurs : Bàrbara TORRICO, Auteur ; Andreas G. CHIOCCHETTI, Auteur ; Elena BACCHELLI, Auteur ; Elisabetta TRABETTI, Auteur ; Amaia HERVAS, Auteur ; Barbara FRANKE, Auteur ; Jan K. BUITELAAR, Auteur ; Nanda N. ROMMELSE, Auteur ; Afsheen YOUSAF, Auteur ; Eftichia DUKETIS, Auteur ; Christine M. FREITAG, Auteur ; Rafaela CABALLERO-ANDALUZ, Auteur ; Amalia MARTINEZ-MIR, Auteur ; Francisco G. SCHOLL, Auteur ; Marta RIBASES, Auteur ; ITAN, Auteur ; Agatino BATTAGLIA, Auteur ; Giovanni MALERBA, Auteur ; Richard DELORME, Auteur ; Marion BENABOU, Auteur ; Elena MAESTRINI, Auteur ; Thomas BOURGERON, Auteur ; Bru CORMAND, Auteur ; Claudio TOMA, Auteur Article en page(s) : p.202-211 Langues : Anglais (eng) Mots-clés : genome-wide association study  replication  autism spectrum disorder  European populations  MACROD2  SEMA5A  MSNP1 Index. décimale : PER Périodiques Résumé : Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI?=?0.84–1.32) for rs10513025, 1.0002 (95% CI?=?0.93–1.08) for rs4141463 and 1.01 (95% CI?=?0.92–1.1) for rs4307059, with no significant P-values (rs10513025, P?=?0.73; rs4141463, P?=?0.95; rs4307059, P?=?0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. En ligne : http://dx.doi.org/10.1002/aur.1662 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Lack of replication of previous autism spectrum disorder GWAS hits in European populations [Texte imprimé et/ou numérique] / Bàrbara TORRICO, Auteur ; Andreas G. CHIOCCHETTI, Auteur ; Elena BACCHELLI, Auteur ; Elisabetta TRABETTI, Auteur ; Amaia HERVAS, Auteur ; Barbara FRANKE, Auteur ; Jan K. BUITELAAR, Auteur ; Nanda N. ROMMELSE, Auteur ; Afsheen YOUSAF, Auteur ; Eftichia DUKETIS, Auteur ; Christine M. FREITAG, Auteur ; Rafaela CABALLERO-ANDALUZ, Auteur ; Amalia MARTINEZ-MIR, Auteur ; Francisco G. SCHOLL, Auteur ; Marta RIBASES, Auteur ; ITAN, Auteur ; Agatino BATTAGLIA, Auteur ; Giovanni MALERBA, Auteur ; Richard DELORME, Auteur ; Marion BENABOU, Auteur ; Elena MAESTRINI, Auteur ; Thomas BOURGERON, Auteur ; Bru CORMAND, Auteur ; Claudio TOMA, Auteur . - p.202-211. Langues : Anglais (eng) in Autism Research > 10-2 (February 2017) . - p.202-211 Mots-clés : genome-wide association study  replication  autism spectrum disorder  European populations  MACROD2  SEMA5A  MSNP1 Index. décimale : PER Périodiques Résumé : Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI?=?0.84–1.32) for rs10513025, 1.0002 (95% CI?=?0.93–1.08) for rs4141463 and 1.01 (95% CI?=?0.92–1.1) for rs4307059, with no significant P-values (rs10513025, P?=?0.73; rs4141463, P?=?0.95; rs4307059, P?=?0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. En ligne : http://dx.doi.org/10.1002/aur.1662 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder / Sören MERKER in Journal of Child Psychology and Psychiatry, 58-7 (July 2017)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 58-7 (July 2017) . - p.798-809 Titre : SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder Type de document : Texte imprimé et/ou numérique Auteurs : Sören MERKER, Auteur ; Andreas REIF, Auteur ; Georg C. ZIEGLER, Auteur ; Heike WEBER, Auteur ; Ute MAYER, Auteur ; Ann-Christine EHLIS, Auteur ; Annette CONZELMANN, Auteur ; Stefan JOHANSSON, Auteur ; Clemens MÜLLER-REIBLE, Auteur ; Indrajit NANDA, Auteur ; Thomas HAAF, Auteur ; Reinhard ULLMANN, Auteur ; Marcel ROMANOS, Auteur ; Andreas J. FALLGATTER, Auteur ; Paul PAULI, Auteur ; Tatyana STREKALOVA, Auteur ; Charline JANSCH, Auteur ; Alejandro ARIAS-VASQUEZ, Auteur ; Jan HAAVIK, Auteur ; Marta RIBASES, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Jan K. BUITELAAR, Auteur ; Barbara FRANKE, Auteur ; Klaus-Peter LESCH, Auteur Article en page(s) : p.798-809 Langues : Anglais (eng) Mots-clés : Attention-deficit/hyperactivity disorder  glucose transporter  SLC2A3  single-nucleotide polymorphisms  duplication  copy number variants  energy homeostasis  frontostriatal network Index. décimale : PER Périodiques Résumé : Background Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods Case–control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. En ligne : http://dx.doi.org/10.1111/jcpp.12702 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=316 [article] SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder [Texte imprimé et/ou numérique] / Sören MERKER, Auteur ; Andreas REIF, Auteur ; Georg C. ZIEGLER, Auteur ; Heike WEBER, Auteur ; Ute MAYER, Auteur ; Ann-Christine EHLIS, Auteur ; Annette CONZELMANN, Auteur ; Stefan JOHANSSON, Auteur ; Clemens MÜLLER-REIBLE, Auteur ; Indrajit NANDA, Auteur ; Thomas HAAF, Auteur ; Reinhard ULLMANN, Auteur ; Marcel ROMANOS, Auteur ; Andreas J. FALLGATTER, Auteur ; Paul PAULI, Auteur ; Tatyana STREKALOVA, Auteur ; Charline JANSCH, Auteur ; Alejandro ARIAS-VASQUEZ, Auteur ; Jan HAAVIK, Auteur ; Marta RIBASES, Auteur ; Josep Antoni RAMOS-QUIROGA, Auteur ; Jan K. BUITELAAR, Auteur ; Barbara FRANKE, Auteur ; Klaus-Peter LESCH, Auteur . - p.798-809. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 58-7 (July 2017) . - p.798-809 Mots-clés : Attention-deficit/hyperactivity disorder  glucose transporter  SLC2A3  single-nucleotide polymorphisms  duplication  copy number variants  energy homeostasis  frontostriatal network Index. décimale : PER Périodiques Résumé : Background Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory–inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Methods Case–control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Results Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Conclusions Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. En ligne : http://dx.doi.org/10.1111/jcpp.12702 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=316

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