Attention-deficit hyperactivity disorder is a highly inherited neurodevelopmental disorder. Previous genetic research has linked ADHD to certain genes in the dopaminergic synaptic pathway. Nonetheless, research on this relationship has produced varying results across various populations. China is a multi-ethnic country with its own unique genetic characteristics. Therefore, such a population can provide useful information about the relationship between gene polymorphisms in dopaminergic synaptic pathways and ADHD. This study looked at the genetic profiles of 284 children in China’s Xinjiang. In total, 142 ADHD children and 142 control subjects were enrolled. Following the extraction of DNA from oral mucosal cells, 13 SNPs for three candidate genes (SLC6A3, DRD2, and GRIN2B) in the dopaminergic synaptic pathway of ADHD were screened. Based on the results of single nucleotide polymorphism (SNP) analyses, we found that the DRD2 gene variants rs6277 and rs6275, and the SLC6A3 gene variant rs2652511, were significantly associated with ADHD in boys and girls, respectively, after adjusting for false discovery rate (FDR) in terms of allele frequencies. Furthermore, our generalized multifactorial downscaling approach identified a significant association between rs6275 and rs1012586. These findings suggest that DRD2 and SLC6A3 genes have a crucial role in ADHD susceptibility. Additionally, we observed that the interaction between GRIN2B and DRD2 genes may contribute to the susceptibility of Chinese children with ADHD.
Background Attention deficit hyperactivity disorder (ADHD) is in a close correlation with developmental dyslexia (DD), which are both prevalent and complicated pediatric neurodevelopmental disorders that significantly affect the learning and development of children. Clinically, the comorbidity incidence of DD and ADHD is between 25 and 48%. Children with DD and ADHD may have more severe cognitive deficiencies, a poorer level of schooling, and a higher risk of social and emotional management disorders. Furthermore, patients with this comorbidity are frequently treated for a single condition in clinical settings, and the therapeutic outcome is poor. The development of efficient therapies for the diseases turns sophisticated due to their comorbidity characteristics. It has long been a critical issue in diagnosis and treatment. In the current research, bioinformatical methodology was developed to analyze the comorbidity of the two diseases. Therefore, finding candidate genes associated with comorbid conditions of ADHD and DD contributes to interpretation of the molecular mechanisms in comorbid conditions, genotype and identification of novel drug targets. Results With the ANDSystem tool, gene networks related to ADHD and dyslexia were reconstructed and analyzed. The gene network for ADHD contained 599 genes/proteins and 148978 interactions, and that for dyslexia contained 167 genes/proteins and 27083 interactions. When the ANDSystem and GeneCard data were combined, a total of 213 genes/proteins for ADHD and dyslexia were found. A method that could rank genes in comorbid conditions of these two diseases was presented. This method followed 10 criteria of ranking genes based on importance, such as relevance scores of association between disease and genes, standard gene prioritization methods, and original criteria considering the features in an associative gene network and known polymorphisms of the analyzed genes. With the presented method, genes OPRM1, CHRNA4 and SNCA were found to have the highest priority in developing comorbidity of the two diseases. In addition, research showed the involvement of the most relevant genes in biological processes associated with signal transduction, positive regulation of transcription from RNA polymerase II promoters, chemical synaptic transmission, response to drugs, ion transmembrane transport, nervous system development, cell adhesion, as well as neuron migration. Conclusions Gene network reconstruction and analysis methods can be used in the study on the molecular mechanisms in comorbid conditions. The proposed method ranking genes based on importance in comorbid conditions of ADHD and dyslexia was used to predict genes that play key roles in the development of the comorbid condition. The findings provide a reference for experiments conducted to identify new candidate genes and find new pharmacological targets.
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