scholarly journals Cross-disorder risk gene CACNA1C differentially modulates susceptibility to psychiatric disorders during development and adulthood

2017 ◽  
Vol 23 (3) ◽  
pp. 533-543 ◽  
Author(s):  
N Dedic ◽  
M L Pöhlmann ◽  
J S Richter ◽  
D Mehta ◽  
D Czamara ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Risk Gene ◽  
Disorder Risk

scholarly journals Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes

Neuroscience ◽  
2010 ◽  
Vol 168 (3) ◽  
pp. 797-810 ◽  
Author(s):  
K.L. Eagleson ◽  
M.C. Gravielle ◽  
L.J. Schlueter McFadyen-Ketchum ◽  
S.J. Russek ◽  
D.H. Farb ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gabaa Receptor ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Receptor Subunit ◽  
Risk Gene ◽  
Autism Spectrum Disorder Risk ◽  
Disorder Risk

No evidence for association between bipolar disorder risk gene variants and brain structural phenotypes

2013 ◽  
Vol 151 (1) ◽  
pp. 291-297 ◽  
Author(s):  
Martin Tesli ◽  
Randi Egeland ◽  
Ida E. Sønderby ◽  
Unn K. Haukvik ◽  
Francesco Bettella ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Gene Variants ◽  
Risk Gene ◽  
Disorder Risk

scholarly journals Bipolar disorder risk gene FOXO6 modulates negative symptoms in schizophrenia: a neuroimaging genetics study

2017 ◽  
Vol 42 (3) ◽  
pp. 172-180 ◽  
Author(s):  
Joseph J. Shenker ◽  
Sarojini M. Sengupta ◽  
Ridha Joober ◽  
Ashok Malla ◽  
M. Mallar Chakravarty ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Negative Symptoms ◽  
Risk Gene ◽  
Neuroimaging Genetics ◽  
Disorder Risk

scholarly journals Genome-wide landscape of RNA-binding protein dysregulation reveals a major impact on psychiatric disorder risk

2020 ◽  
Author(s):  
Christopher Y. Park ◽  
Jian Zhou ◽  
Aaron K. Wong ◽  
Kathleen M. Chen ◽  
Chandra L. Theesfeld ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Large Scale ◽  
Complex Disease ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Full Range ◽  
Coding Region ◽  
Genome Wide ◽  
Disorder Risk

AbstractDespite the strong genetic basis of psychiatric disorders, the molecular origins of these diseases are still largely unmapped. RNA-binding proteins (RBPs) are responsible for most post-transcriptional regulation, from splicing to translational to localization. RBPs thus act as key gatekeepers of cellular homeostasis, especially in the brain. Here, we leverage a deep learning approach to interrogate variant effects genome-wide, and discover that the dysregulation of RBP target sites is a principal contributor to psychiatric disorder risk. We show that specific modes of RBP regulation are genetically linked to the heritability of psychiatric disorders, and demonstrate that diverse RBP regulatory functions are reflected in distinct genome-wide negative selection signatures. Notably, RBP dysregulation has a stronger impact on psychiatric disorders than common coding region variants and explains heritability not currently captured by large-scale molecular QTL studies (expression QTLs and splicing QTLs). We share genome-wide profiles of RBP target site dysregulation, which we used to identify DDHD2 as a candidate schizophrenia risk gene, in a public web server. This resource provides a novel analytical framework to connect the full range of RNA regulation to complex disease.

scholarly journals Integrating brain methylome with GWAS for psychiatric risk gene discovery

2018 ◽  
Author(s):  
Shizhong Han ◽  
Ying Lin ◽  
Minghui Wang ◽  
Fernando S. Goes ◽  
Kai Tan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Human Brain ◽  
Association Study ◽  
Psychiatric Disorders ◽  
Gene Discovery ◽  
Cpg Sites ◽  
Risk Gene ◽  
Risk Variants ◽  
Trait Associations

AbstractDNA methylation (DNAm) is heritable and plays a role in brain development and function through transcriptional regulation. Aberrant DNAm in human brain has been linked to psychiatric disorders, potentially as mediators of common genetic risk variants. In this study, we hypothesize that common risk variants for psychiatric disorders may act through affecting DNAm level in human brain. We first aimed to investigate the heritability pattern of DNAm levels in the human prefrontal cortex. Secondly, through imputation-driven methylome-wide association study (MWAS), we aimed to identify CpG sites whose methylation levels are genetically associated and that show methylation-trait associations in the prefrontal cortex of patients with schizophrenia or bipolar disorder. Our heritability analysis showed that, of ~370,000 CpG sites measured with the Illumina HumanMethylation450 microarray, 17% were heritable (p < 0.05), with a mean heritability of 0.22. Heritable CpG sites were enriched in intergenic regions, CpG shore, and regulatory regions in prefrontal cortex. Our MWAS approach identified known and potentially novel risk genes harboring CpG sites of methylation-trait associations for schizophrenia or bipolar disorder, which were not detectable using three alternative strategies (blood-based methylome reference, transcriptome-wide association study, and two gene-based association tests). Gene set enrichment analysis for genes with methylation-trait association evidence revealed pathways clearly related to neuronal functions, but also highlighted additional biological mechanisms that may underlie psychiatric disorders, such as microRNA-related regulation. In conclusion, our results showed the power of integrating brain methylation data with GWAS for psychiatric risk gene discovery, with potential applications in brain-related disorders or traits.

scholarly journals Interplay between a Mental Disorder Risk Gene and Developmental Polarity Switch of GABA Action Leads to Excitation-Inhibition Imbalance

Cell Reports ◽  
2019 ◽  
Vol 28 (6) ◽  
pp. 1419-1428.e3 ◽  
Author(s):  
Eunchai Kang ◽  
Juan Song ◽  
Yuting Lin ◽  
Jaesuk Park ◽  
Jennifer H. Lee ◽  
...  
Keyword(s):  
Mental Disorder ◽  
Risk Gene ◽  
Polarity Switch ◽  
Disorder Risk

scholarly journals Social Behavior and Ultrasonic Vocalizations in a Genetic Rat Model Haploinsufficient for the Cross-Disorder Risk Gene Cacna1c

2021 ◽  
Vol 11 (6) ◽  
pp. 724
Author(s):  
Markus Wöhr ◽  
Theresa M. Kisko ◽  
Rainer K.W. Schwarting
Keyword(s):  
Social Behavior ◽  
Rat Model ◽  
Ultrasonic Vocalizations ◽  
Social Signals ◽  
Affective Communication ◽  
Risk Gene ◽  
The Cross ◽  
Behavioral Characterization ◽  
Disorder Risk

The top-ranked cross-disorder risk gene CACNA1C is strongly associated with multiple neuropsychiatric dysfunctions. In a recent series of studies, we applied a genomically informed approach and contributed extensively to the behavioral characterization of a genetic rat model haploinsufficient for the cross-disorder risk gene Cacna1c. Because deficits in processing social signals are associated with reduced social functioning as commonly seen in neuropsychiatric disorders, we focused on socio-affective communication through 22-kHz and 50-kHz ultrasonic vocalizations (USV). Specifically, we applied a reciprocal approach for studying socio-affective communication in sender and receiver by including rough-and-tumble play and playback of 22-kHz and 50-kHz USV. Here, we review the findings obtained in this recent series of studies and link them to the key features of 50-kHz USV emission during rough-and-tumble play and social approach behavior evoked by playback of 22-kHz and 50-kHz USV. We conclude that Cacna1c haploinsufficiency in rats leads to robust deficits in socio-affective communication through 22-kHz and 50-kHz USV and associated alterations in social behavior, such as rough-and-tumble play behavior.

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