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https://doi.org/10.1038/tp.2016.273
Title: | Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: Association to overlapping traits in ADHD and autism | Authors: | Naaijen J. Bralten J. Poelmans G. Glennon J.C. Franke B. Buitelaar J.K. Faraone S. Asherson P. Banaschewski T. P Ebstein R. Gill M. Miranda A. Oades R.D. Roeyers H. Rothenberger A. Sergeant J. Sonuga-Barke E. Anney R. Mulas F. Steinhausen H.-C. The Image Consortium |
Keywords: | 4 aminobutyric acid glutamic acid neurotransmitter 4 aminobutyric acid 4 aminobutyric acid A receptor AMPA receptor calcium binding protein CALML5 protein, human CD98 antigen GABRA3 protein, human GABRE protein, human GABRQ protein, human glutamate receptor ionotropic, AMPA 3 glutamic acid GRIN1 protein, human metabotropic receptor metabotropic receptor 2 n methyl dextro aspartic acid receptor nerve protein NMDA receptor A1 SLC7A7 protein, human adolescent adult aged Article attention deficit disorder autism behavior child controlled study disease severity female GABAergic system gene expression gene frequency genetic association genetic risk genetic variability genotype glutamatergic synapse human major clinical study male multicenter study neurotransmission single nucleotide polymorphism X chromosome attention deficit disorder autism genetics metabolism preschool child psychology severity of illness index Adolescent Attention Deficit Disorder with Hyperactivity Autism Spectrum Disorder Autistic Disorder Calcium-Binding Proteins Child Child, Preschool Female Fusion Regulatory Protein 1, Light Chains gamma-Aminobutyric Acid Glutamic Acid Humans Male Nerve Tissue Proteins Receptors, AMPA Receptors, GABA-A Receptors, Metabotropic Glutamate Receptors, N-Methyl-D-Aspartate Severity of Illness Index |
Issue Date: | 2017 | Citation: | Naaijen J., Bralten J., Poelmans G., Glennon J.C., Franke B., Buitelaar J.K., Faraone S., Asherson P., Banaschewski T., P Ebstein R., Gill M., Miranda A., Oades R.D., Roeyers H., Rothenberger A., Sergeant J., Sonuga-Barke E., Anney R., Mulas F., Steinhausen H.-C., The Image Consortium (2017). Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: Association to overlapping traits in ADHD and autism. Translational Psychiatry 7 (1) : 273. ScholarBank@NUS Repository. https://doi.org/10.1038/tp.2016.273 | Abstract: | Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously. Common variants within glutamatergic and GABAergic genes were investigated using the MAGMA software in an ADHD case-only sample (n = 931), in which we assessed ASD symptoms and response inhibition on a Stop task. Gene set analysis for ADHD symptom severity, divided into inattention and hyperactivity/impulsivity symptoms, autism symptom severity and inhibition were performed using principal component regression analyses. Subsequently, gene-wide association analyses were performed. The glutamate gene set showed an association with severity of hyperactivity/impulsivity (P = 0.009), which was robust to correcting for genome-wide association levels. The GABA gene set showed nominally significant association with inhibition (P = 0.04), but this did not survive correction for multiple comparisons. None of single gene or single variant associations was significant on their own. By analyzing multiple genetic variants within candidate gene sets together, we were able to find genetic associations supporting the involvement of excitatory and inhibitory neurotransmitter systems in ADHD and ASD symptom severity in ADHD. © The Author(s) 2017. | Source Title: | Translational Psychiatry | URI: | https://scholarbank.nus.edu.sg/handle/10635/174618 | ISSN: | 2158-3188 | DOI: | 10.1038/tp.2016.273 |
Appears in Collections: | Elements Staff Publications |
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