scholarly journals Non-coding structural variation differentially impacts attention-deficit hyperactivity disorder (ADHD) gene networks in African American vs Caucasian children

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yichuan Liu ◽  
Xiao Chang ◽  
Huiqi Qu ◽  
Joseph Glessner ◽  
Lifeng Tian ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Whole Genome Sequence ◽  
European Ancestry ◽  
Receptor Interaction ◽  
Hyperactivity Disorder ◽  
Coding Regions

Abstract Previous studies of attention-deficit hyperactivity disorder (ADHD) have suggested that structural variants (SVs) play an important role but these were mainly studied in subjects of European ancestry and focused on coding regions. In this study, we sought to address the role of SVs in non-European populations and outside of coding regions. To that end, we generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The ADHD cases included 116 African Americans (AA) and 89 of European Ancestry (EA) with SVs in comparison with 408 AA and 262 controls, respectively. Multiple SVs and target genes that associated with ADHD from previous studies were identified or replicated, and novel recurrent ADHD-associated SV loci were discovered. We identified clustering of non-coding SVs around neuroactive ligand-receptor interaction pathways, which are involved in neuronal brain function, and highly relevant to ADHD pathogenesis and regulation of gene expression related to specific ADHD phenotypes. There was little overlap (around 6%) in the genes impacted by SVs between AA and EA. These results suggest that SVs within non-coding regions may play an important role in ADHD development and that WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD

scholarly journals Rare Recurrent Variants in Noncoding Regions Impact Attention-Deficit Hyperactivity Disorder (ADHD) Gene Networks in Children of both African American and European American Ancestry

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 310
Author(s):  
Yichuan Liu ◽  
Xiao Chang ◽  
Hui-Qi Qu ◽  
Lifeng Tian ◽  
Joseph Glessner ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
Whole Genome Sequence ◽  
Noncoding Regions ◽  
Hyperactivity Disorder ◽  
Significant Impairment

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with poorly understood molecular mechanisms that results in significant impairment in children. In this study, we sought to assess the role of rare recurrent variants in non-European populations and outside of coding regions. We generated whole genome sequence (WGS) data on 875 individuals, including 205 ADHD cases and 670 non-ADHD controls. The cases included 116 African Americans (AA) and 89 European Americans (EA), and the controls included 408 AA and 262 EA. Multiple novel rare recurrent variants were identified in exonic regions, functionally classified as stop-gains and frameshifts for known ADHD genes. Deletion in introns of the protocadherins families and the ncRNA HGB8P were identified in two independent EA ADHD patients. A meta-analysis of the two ethnicities for differential ADHD recurrent variants compared to controls shows a small number of overlaps. These results suggest that rare recurrent variants in noncoding regions may be involved in the pathogenesis of ADHD in children of both AA and EA ancestry; thus, WGS could be a powerful discovery tool for studying the molecular mechanisms of ADHD.

Vitamin D’s Molecular Action Mechanism in Attention-Deficit/ Hyperactivity Disorder: A Review of Evidence

2018 ◽  
Vol 17 (4) ◽  
pp. 280-290 ◽  
Author(s):  
Ahmad Saedisomeolia ◽  
Mahsa Samadi ◽  
Fatemeh Gholami ◽  
Marzieh Seyedi ◽  
Mohammad Effatpanah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Molecular Mechanisms ◽  
Healthy Children ◽  
Related Factors ◽  
Children With Adhd ◽  
Hyperactivity Disorder ◽  
Vitamin D Levels

Background & Objective: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder characterized by hyperactivity, impulsivity and inattention. Children with ADHD have challenges with learning, behavior and psychosocial adjustments, sometimes retained into adulthood. The exact etiology of ADHD is unknown, and the pathophysiology of this disease is complex. Several hypotheses have been raised regarding ADHD pathogenesis, including serotonergic and catecholaminergic signalling pathway dysfunction, neurotropic-related factors, oxidative stress, or neuroinflammation. Vitamin D has an important protective effect against inflammation, oxidative stress and certain neurotrophic factors and neurotransmitter, as well as facilitating dopaminergic and serotonergic functions. Vitamin D levels in children with ADHD are lower than in healthy children, and thus may be involved in the pathogenesis of ADHD. These observations, therefore, confirm the neuroprotective role of vitamin D through multiple molecular mechanisms and can be considered as a promising target in understanding ADHD pathology. Conclusion: In this context, the present study reviews the molecular pathways of vitamin D in ADHD patients.

scholarly journals A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder

2020 ◽  
Author(s):  
Lars Libuda ◽  
Roaa Naaresh ◽  
Christine Ludwig ◽  
Björn-Hergen Laabs ◽  
Jochen Antel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
European Ancestry ◽  
Inverse Association ◽  
Hyperactivity Disorder ◽  
25 Oh Vitamin D ◽  
Mr Study

Abstract Background While observational studies revealed an inverse association between serum 25(OH)vitamin D (25(OH)D) and the risk of attention deficit/hyperactivity disorder (ADHD), the causality of this relationship remains unclear. Methods We conducted a bidirectional two-sample Mendelian Randomization (MR) study to examine whether 25(OH)D has an effect on the risk to develop ADHD or vice versa. Information on single nucleotide polymorphisms (SNP) associated with serum 25(OH)D was obtained from a genome-wide association study (GWAS) considering phenotype data from 79,366 individuals of European ancestry. Data on risk for ADHD were derived from a GWAS analysis with 20,183 individuals diagnosed with ADHD and 35,191 controls. For our analysis, we considered effect sizes based on the European participants (19,099 cases and 34,194 controls). Results Single SNP analyses showed a causal effect of vitamin D on ADHD risk for only one SNP (rs12785878, p = 0.024). The overall MR estimates did not reveal a causal effect of 25(OH)D on risk for ADHD. In the reverse analysis, neither any single nor the multi-SNP MR analyses showed a causal effect of ADHD on 25(OH)D. Conclusion Results from this two-sample MR study did not confirm a causal effect of 25(OH)D on ADHD or vice versa. Accordingly, our study does not provide evidence that improving 25(OH)D via supplementation could reduce the risk of developing ADHD.

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