Whole-Exome Sequencing Reveals Increased Burden of Rare Functional and Disruptive Variants in Candidate Risk Genes in Individuals With Persistent Attention-Deficit/Hyperactivity Disorder

2016 ◽  
Vol 55 (6) ◽  
pp. 521-523 ◽  
Author(s):  
Ditte Demontis ◽  
Francesco Lescai ◽  
Anders Børglum ◽  
Simon Glerup ◽  
Søren Dinesen Østergaard ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Attention Deficit ◽  
Risk Genes ◽  
Hyperactivity Disorder ◽  
Whole Exome

scholarly journals Whole Exome Sequencing: Novel Genetic Polymorphisms in Saudi Arabian Attention Deficit Hyperactivity Disorder (ADHD) Children

2019 ◽  
Vol 11 (02) ◽  
pp. 45-60
Author(s):  
Neda Mostafa Bogari ◽  
Amr Ahmed Amin ◽  
Ashwag Aljohani ◽  
Ghida Dairi ◽  
Mahmoud Zaki El-Readi ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Exome Sequencing ◽  
Genetic Polymorphisms ◽  
Whole Exome Sequencing ◽  
Attention Deficit ◽  
Saudi Arabian ◽  
Hyperactivity Disorder ◽  
Whole Exome ◽  
Adhd Children

scholarly journals Preferential Transmission of Paternal Alleles at Risk Genes in Attention-Deficit/Hyperactivity Disorder

2005 ◽  
Vol 77 (6) ◽  
pp. 958-965 ◽  
Author(s):  
Ziarih Hawi ◽  
Ricardo Segurado ◽  
Judith Conroy ◽  
Karen Sheehan ◽  
Naomi Lowe ◽  
...  
Keyword(s):  
At Risk ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Risk Genes ◽  
Preferential Transmission ◽  
Hyperactivity Disorder

scholarly journals Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

2020 ◽  
Author(s):  
Holly K. Harris ◽  
Tojo Nakayama ◽  
Jenny Lai ◽  
Boxun Zhao ◽  
Nikoleta Argyrou ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Transcription Factors ◽  
Intellectual Disability ◽  
Attention Deficit ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Risk Genes ◽  
Hyperactivity Disorder

Purpose: We describe a novel neurobehavioral syndrome of autism spectrum disorder, intellectual disability, and attention deficit/hyperactivity disorder associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods: We assembled a cohort of 36 individuals (from 31 unrelated families) with de novo mutations in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results: These individuals share neurobehavioral features including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD); other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion: These results establish deleterious variation in RFX3, RFX4, and RFX7 as important causes of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

scholarly journals De novo damaging coding mutations are strongly associated with obsessive-compulsive disorder and overlap with autism

2017 ◽  
Author(s):  
Carolina Cappi ◽  
Melody E. Oliphant ◽  
Zsanett Péter ◽  
Gwyneth Zai ◽  
Catherine A. W. Sullivan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Obsessive Compulsive Disorder ◽  
Whole Exome Sequencing ◽  
Strong Evidence ◽  
De Novo ◽  
High Confidence ◽  
Obsessive Compulsive ◽  
Risk Genes ◽  
Compulsive Disorder ◽  
Whole Exome

ABSTRACTObsessive-compulsive disorder (OCD) is a debilitating developmental neuropsychiatric disorder with a genetic risk component, yet identification of high-confidence risk genes has been challenging. We performed whole-exome sequencing in 222 OCD parent-child trios (184 trios after quality control), finding strong evidence that de novo likely gene disrupting and predicted damaging missense variants contribute to OCD risk. Together, these de novo damaging variants are enriched in OCD probands (RR 1.52, p=0.0005). We identified two high-confidence risk genes, each containing two de novo damaging variants in unrelated probands: CHD8 (Chromodomain Helicase DNA Binding Protein 8) and SCUBE1 (Signal Peptide, CUB Domain And EGF Like Domain Containing 1). Based on our data, we estimate that 34% of de novo damaging variants seen in OCD contribute to risk, and that de novo damaging variants in approximately 335 genes contribute to risk in 22% of OCD cases. Furthermore, genes harboring de novo damaging variants in OCD are enriched for those reported in neurodevelopmental disorders, particularly autism spectrum disorders. An exploratory network analysis reveals significant functional connectivity and enrichment in canonical pathways related to immune response.SIGNIFICANCE STATEMENTDecades of genetic studies in obsessive-compulsive disorder (OCD) have yet to provide reproducible, statistically significant findings. Following an approach that has led to tremendous success in gene discovery for several neuropsychiatric disorders, here we report findings from DNA whole-exome sequencing of patients with OCD and their parents. We find strong evidence for the contribution of spontaneous, or de novo, predicted-damaging genetic variants to OCD risk, identify two high-confidence risk genes, and detect significant overlap with genes previously identified in autism. These results change the status quo of OCD genetics by identifying novel OCD risk genes, clarifying the genetic landscape of OCD with respect to de novo variation, and suggesting underlying biological pathways that will improve our understanding of OCD biology.

scholarly journals Identification of Autism Risk Genes in a Chinese Cohort via Whole-Exome Sequencing with the Joint Calling Analysis

2020 ◽  
Author(s):  
Bo Yuan ◽  
Peipei Cheng ◽  
Ran Zhang ◽  
Yasong Du ◽  
Zilong Qiu
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
East Asian ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Large Sample Size ◽  
Risk Genes ◽  
Genetic Components ◽  
Whole Exome

Abstract Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation, transcriptional regulation, and chromatin remodeling, have been identified, the genetic analysis on east Asian ASD cohorts in the whole-geome or whole-exome level is still limited(1-5). Here we performed whole-exome sequencing on 168 ASD probands with their unaffected parents of Chinese origin. We applied a joint calling analytical pipeline based on GATK best practices and identified numerous de novo variants including single nucleotide variants (SNVs) and insertion or deletions (INDELs). By querying the Simons foundation autism research initiative (SFARI) gene database, we found that there were potential novel ASD risk genes in East Asian cohorts, which did not exist in European American populations. Furthermore, our analysis pipeline identified de novo copy number variations (CNVs) of known ASD-related gene based on a sufficiently large sample size, validated by quantitative PCR. Our work indicated that there may be differences in potential ASD genetic components existing across different geographical populations, suggesting that genomic analysis over large cohorts are required for each population in order to precisely identify ASD risk genes.

scholarly journals Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing

2018 ◽  
Vol 25 (9) ◽  
pp. 2047-2057 ◽  
Author(s):  
Jordi Corominas ◽  
Marieke Klein ◽  
Tetyana Zayats ◽  
Olga Rivero ◽  
Georg C. Ziegler ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Risk Genes ◽  
Extended Pedigrees ◽  
Whole Exome
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