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Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8-29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.
Pubmed ID: 37378697 RIS Download
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Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware library of image analysis and statistical tools for fMRI, MRI and DTI brain imaging data. Include registration, atlases, diffusion MRI tools for parameter reconstruction and probabilistic taractography, and viewer. Several brain atlases, integrated into FSLView and Featquery, allow viewing of structural and cytoarchitectonic standard space labels and probability maps for cortical and subcortical structures and white matter tracts. Includes Harvard-Oxford cortical and subcortical structural atlases, Julich histological atlas, JHU DTI-based white-matter atlases, Oxford thalamic connectivity atlas, Talairach atlas, MNI structural atlas, and Cerebellum atlas.
View all literature mentionsA dataset containing the full genomic sequence of 1,700 individuals, freely available for research use. The 1000 Genomes Project is an international research effort coordinated by a consortium of 75 companies and organizations to establish the most detailed catalogue of human genetic variation. The project has grown to 200 terabytes of genomic data including DNA sequenced from more than 1,700 individuals that researchers can now access on AWS for use in disease research free of charge. The dataset containing the full genomic sequence of 1,700 individuals is now available to all via Amazon S3. The data can be found at: http://s3.amazonaws.com/1000genomes The 1000 Genomes Project aims to include the genomes of more than 2,662 individuals from 26 populations around the world, and the NIH will continue to add the remaining genome samples to the data collection this year. Public Data Sets on AWS provide a centralized repository of public data hosted on Amazon Simple Storage Service (Amazon S3). The data can be seamlessly accessed from AWS services such Amazon Elastic Compute Cloud (Amazon EC2) and Amazon Elastic MapReduce (Amazon EMR), which provide organizations with the highly scalable compute resources needed to take advantage of these large data collections. AWS is storing the public data sets at no charge to the community. Researchers pay only for the additional AWS resources they need for further processing or analysis of the data. All 200 TB of the latest 1000 Genomes Project data is available in a publicly available Amazon S3 bucket. You can access the data via simple HTTP requests, or take advantage of the AWS SDKs in languages such as Ruby, Java, Python, .NET and PHP. Researchers can use the Amazon EC2 utility computing service to dive into this data without the usual capital investment required to work with data at this scale. AWS also provides a number of orchestration and automation services to help teams make their research available to others to remix and reuse. Making the data available via a bucket in Amazon S3 also means that customers can crunch the information using Hadoop via Amazon Elastic MapReduce, and take advantage of the growing collection of tools for running bioinformatics job flows, such as CloudBurst and Crossbow.
View all literature mentionsMarkov chain Monte Carlo program for association in two-dimensional contingency tables, and for testing Hardy-Weinberg equilibrium. (entry from Genetic Analysis Software)
View all literature mentionsCommercial neuroimaging organization that provides services for compound profiling, biostatistics, computed tomography, and data modeling.
View all literature mentionsSoftware R package for calculating, applying, evaluating and plotting results of polygenic risk scores analysis. Performs simulation study to estimate P value significance threshold for high resolution PRS studies and produces plots for inspection of results. Operating Unix/Linux.
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