The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence

Zhu, Bi; Chen, Chuansheng; Xue, Gui; Lei, Xin; Li, Jin; Moyzis, Robert K.; Dong, Qinglin; Lin, Chongde

doi:10.1016/j.neuroimage.2014.08.048

Cited by 11 publications

(10 citation statements)

References 59 publications

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“…GABRB1 (gamma-aminobutyric acid type A receptor beta1 subunit) gene encodes for beta 1 subunit of the GABA A receptor, which is responsible for mediating inhibitory neurotransmission in the thalamus [51]. A previous report shows its role in alveolar fluid homeostasis of alveolar epithelial type II cells [52].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD

et al. 2017

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BackgroundEpigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from parenchymal lung tissues of patients including eight lifelong non-smokers, eight current smokers, and eight patients with COPD and analyzed the samples using Illumina’s Infinium HumanMethylation450 BeadChip.ResultsOur data revealed that the differentially methylated genes were related to top canonical pathways (e.g., G beta gamma signaling, mechanisms of cancer, and nNOS signaling in neurons), disease and disorders (organismal injury and abnormalities, cancer, and respiratory disease), and molecular and cellular functions (cell death and survival, cellular assembly and organization, cellular function and maintenance) in patients with COPD. The genome-wide DNA methylation analysis identified suggestive genes, such as NOS1AP, TNFAIP2, BID, GABRB1, ATXN7, and THOC7 with DNA methylation changes in COPD lung tissues that were further validated by pyrosequencing. Pyrosequencing validation confirmed hyper-methylation in smokers and patients with COPD as compared to non-smokers. However, we did not detect significant differences in DNA methylation for TNFAIP2, ATXN7, and THOC7 genes in smokers and COPD groups despite the changes observed in the genome-wide analysis.ConclusionsOur study suggests that DNA methylation in suggestive genes, such as NOS1AP, BID, and GABRB1 may be used as epigenetic signatures in smokers and patients with COPD if the same is validated in a larger cohort. Future studies are required to correlate DNA methylation status with transcriptomics of selective genes identified in this study and elucidate their role and involvement in the progression of COPD and its exacerbations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0335-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD

et al. 2017

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“…Among those top 25 mutations, two mutations were not reported as functional in the original study. One was on gene GABRB1, which was recently proved to be associated with thalamus volume and intelligence [59]. The other one was on gene GNAO1, which was also recently reported to play a significant role in epileptic encephalopathy [60, 61].…”

Section: Resultsmentioning

confidence: 99%

Global inference of disease-causing single nucleotide variants from exome sequencing data

Chen

Jiang

2016

BMC Bioinformatics

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BackgroundWhole exome sequencing (WES) has recently emerged as an effective approach for identifying genetic variants underlying human diseases. However, considerable time and labour is needed for careful investigation of candidate variants. Although filtration based on population frequencies and functional prediction scores could effectively remove common and neutral variants, hundreds or even thousands of rare deleterious variants still remain. In addition, current WES platforms also provide variant information in flanking noncoding regions, such as promoters, introns and splice sites. Despite of being recognized to harbour causal variants, these regions are usually ignored by current analysis pipelines.ResultsWe present a novel computational method, called Glints, to overcome the above limitations. Glints is capable of identifying disease-causing SNVs in both coding and flanking noncoding regions from exome sequencing data. The principle behind Glints is that disease-causing variants should manifest their effect at both variant and gene levels. Specifically, Glints integrates 14 types of functional scores, including predictions for both coding and noncoding variants, and 9 types of association scores, which help identifying disease relevant genes. We conducted a large-scale simulation studies based on 1000 Genomes Project data and demonstrated the effectiveness of our method in both coding and flanking noncoding regions. We also applied Glints in two real exome sequencing and demonstrated its effectiveness for uncovering disease-causing SNVs. Both standalone software and web server are available at our website http://bioinfo.au.tsinghua.edu.cn/jianglab/glints.ConclusionsGlints is effective for uncovering disease-causing SNVs in coding and flanking noncoding regions, which is supported by both simulation and real case studies. Glints is expected to be a useful tool for human genetics research based on exome sequencing data.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1325-x) contains supplementary material, which is available to authorized users.

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“…GABRB1 is a subunit of the gamma-aminobutyric acid A receptor, which is a multi-subunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system [50]. GABRB1 has an important role in the long-term consolidation of precise contextual memories and constrains generalized fear responses [51].…”

Section: Discussionmentioning

confidence: 99%

“…GABRB1 has an important role in the long-term consolidation of precise contextual memories and constrains generalized fear responses [51]. There is also evidence for the involvement of the GABRB1 gene in thalamus volume and interactive effects on intelligence [50]. GABRB1 protein levels were demonstrated to be altered specifically in the superior frontal cortex of subjects with autism [52], and in addictive behaviors, apparently, because it plays a role in the excitability of brain regions important in controlling reward-related behaviors [53].…”

Section: Discussionmentioning

confidence: 99%

Differential Dorsolateral Prefrontal Cortex Proteomic Profiles of Suicide Victims with Mood Disorders

Cabello-Arreola

Özerdem

et al. 2020

Genes

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Suicide is a major public health concern; nevertheless, its neurobiology remains unknown. An area of interest in suicide research is the dorsolateral prefrontal cortex (DLPFC). We aimed to identify altered proteins and potential biological pathways in the DLPFC of individuals who died by suicide employing mass spectrometry-based untargeted proteomics. Postmortem DLPFC from age-matched male suicide mood disorder cases (n = 5) and non-suicide mood disorder cases (n = 5) were compared. The proteins that differed between groups at false discovery rate (FDR) adjusted p-values (Benjamini–Hochberg–Yekutieli) <0.3 and Log2 fold change (FC) >|0.4| were considered statistically significant and were subjected to pathway analysis by Qiagen Ingenuity software. Thirty-three of the 5162 detected proteins showed significantly altered expression levels in the suicide cases and two of them after adjustment for body mass index. The top differentially expressed protein was potassium voltage-gated channel subfamily Q member 3 (KCNQ3) (Log2FC = −0.481, p = 2.10 × 10−09, FDR = 5.93 × 10−06), which also showed a trend to downregulation in Western blot (p = 0.045, Bonferroni adjusted p = 0.090). The most notably enriched pathway was the GABA receptor signaling pathway (p < 0.001). Here, we report a reduction trend of KCNQ3 levels in the DLPFC of male suicide victims with mood disorders. Further studies with a larger sample size and equal sex representation are needed.

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The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence

Cited by 11 publications

References 59 publications

DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD

DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD

Global inference of disease-causing single nucleotide variants from exome sequencing data

Differential Dorsolateral Prefrontal Cortex Proteomic Profiles of Suicide Victims with Mood Disorders

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