Dataset Information

Exploring the relationship between white matter integrity, cocaine use and GAD polymorphisms using Bayesian Model Averaging.

ABSTRACT: Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes, primarily in the corpus callosum. By applying Bayesian model averaging using multiple linear regression in DTI, we demonstrate there may exist relationships between the impaired white matter and glutamic acid decarboxylase (GAD) polymorphisms. This work explored the two-way and three-way interactions between GAD1a (SNP: rs1978340) and GAD1b (SNP: rs769390) polymorphisms and years of cocaine use (YCU). GAD1a was associated with more frontal white matter changes on its own but GAD1b was associated with more midbrain and cerebellar changes as well as a greater increase in white matter changes in the context of chronic cocaine use. The three-way interaction GAD1a|GAD1b|YCU appeared to be roughly an average of the polymorphism two-way interactions GAD1a|YCU and GAD1b|YCU. The three-way interaction demonstrated multiple regions including corpus callosum which featured fewer significant voxel changes, perhaps suggesting a small protective effect of having both polymorphisms on corpus callosum and cerebellar peduncle.

SUBMITTER: Alballa T

PROVIDER: S-EPMC8312937 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Exploring the relationship between white matter integrity, cocaine use and GAD polymorphisms using Bayesian Model Averaging.

Alballa Tmader T Boone Edward L EL Ma Liangsuo L Snyder Andrew A Moeller F Gerard FG

PloS one 20210726 7

Past investigations utilizing diffusion tensor imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes, primarily in the corpus callosum. By applying Bayesian model averaging using multiple linear regression in DTI, we demonstrate there may exist relationships between the impaired white matter and glutamic acid decarboxylase (GAD) polymorphisms. This work explored the two-way and three-way interactions between GAD1a (SNP: rs1978340) and GAD1b (SNP: rs769390) p ...[more]

PMID: 34310624

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Project description:BackgroundDyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type.AimsThis study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions.Patients and methodsThirty-three participants with dyskinetic CP (mean ± SD age: 24.42 ± 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains.ResultsWhite matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum).ConclusionThe widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult.

Project description:BACKGROUND: microRNAs (miRNAs) regulate target gene expression by controlling their mRNAs post-transcriptionally. Increasing evidence demonstrates that miRNAs play important roles in various biological processes. However, the functions and precise regulatory mechanisms of most miRNAs remain elusive. Current research suggests that miRNA regulatory modules are complicated, including up-, down-, and mix-regulation for different physiological conditions. Previous computational approaches for discovering miRNA-mRNA interactions focus only on down-regulatory modules. In this work, we present a method to capture complex miRNA-mRNA interactions including all regulatory types between miRNAs and mRNAs. RESULTS: We present a method to capture complex miRNA-mRNA interactions using Bayesian network structure learning with splitting-averaging strategy. It is designed to explore all possible miRNA-mRNA interactions by integrating miRNA-targeting information, expression profiles of miRNAs and mRNAs, and sample categories. We also present an analysis of data sets for epithelial and mesenchymal transition (EMT). Our results show that the proposed method identified all possible types of miRNA-mRNA interactions from the data. Many interactions are of tremendous biological significance. Some discoveries have been validated by previous research, for example, the miR-200 family negatively regulates ZEB1 and ZEB2 for EMT. Some are consistent with the literature, such as LOX has wide interactions with the miR-200 family members for EMT. Furthermore, many novel interactions are statistically significant and worthy of validation in the near future. CONCLUSIONS: This paper presents a new method to explore the complex miRNA-mRNA interactions for different physiological conditions using Bayesian network structure learning with splitting-averaging strategy. The method makes use of heterogeneous data including miRNA-targeting information, expression profiles of miRNAs and mRNAs, and sample categories. Results on EMT data sets show that the proposed method uncovers many known miRNA targets as well as new potentially promising miRNA-mRNA interactions. These interactions could not be achieved by the normal Bayesian network structure learning.

Dataset Information

Exploring the relationship between white matter integrity, cocaine use and GAD polymorphisms using Bayesian Model Averaging.

Publications

Exploring the relationship between white matter integrity, cocaine use and GAD polymorphisms using Bayesian Model Averaging.

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