Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility

2020 ◽  
pp. 1-12
Author(s):  
Clarice Brinck Brum ◽  
Vanessa Rodrigues Paixão-Côrtes ◽  
Andressa Marques Carvalho ◽  
Thais Martins-Silva ◽  
Marina Xavier Carpena ◽  
...  
Keyword(s):  
Brain Development ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Differentially Expressed

scholarly journals Assessing the Causal Effects of Human Serum Metabolites on 5 Major Psychiatric Disorders

2020 ◽  
Vol 46 (4) ◽  
pp. 804-813 ◽  
Author(s):  
Jian Yang ◽  
Bin Yan ◽  
Binbin Zhao ◽  
Yajuan Fan ◽  
Xiaoyan He ◽  
...  
Keyword(s):  
Human Serum ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Association Studies ◽  
Autism Spectrum ◽  
Causal Effects ◽  
Human Diseases ◽  
Genome Wide Association Studies ◽  
Serum Metabolites ◽  
Intermediate Phenotypes

Abstract Psychiatric disorders are the leading cause of disability worldwide while the pathogenesis remains unclear. Genome-wide association studies (GWASs) have made great achievements in detecting disease-related genetic variants. However, functional information on the underlying biological processes is often lacking. Current reports propose the use of metabolic traits as functional intermediate phenotypes (the so-called genetically determined metabotypes or GDMs) to reveal the biological mechanisms of genetics in human diseases. Here we conducted a two-sample Mendelian randomization analysis that uses GDMs to assess the causal effects of 486 human serum metabolites on 5 major psychiatric disorders, which respectively were schizophrenia (SCZ), major depression (MDD), bipolar disorder (BIP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using genetic variants as proxies, our study has identified 137 metabolites linked to the risk of psychiatric disorders, including 2-methoxyacetaminophen sulfate, which affects SCZ (P = 1.7 × 10–5) and 1-docosahexaenoylglycerophosphocholine, which affects ADHD (P = 5.6 × 10–5). Fourteen significant metabolic pathways involved in the 5 psychiatric disorders assessed were also detected, such as glycine, serine, and threonine metabolism for SCZ (P = .0238), Aminoacyl-tRNA biosynthesis for both MDD (P = .0144) and ADHD (P = .0029). Our study provided novel insights into integrating metabolomics with genomics in order to understand the mechanisms underlying the pathogenesis of human diseases.

scholarly journals The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

2019 ◽  
Vol 25 (2) ◽  
pp. 297-307 ◽  
Author(s):  
Daniel E. Vosberg ◽  
Marco Leyton ◽  
Cecilia Flores
Keyword(s):  
Colorectal Cancer ◽  
Substance Use ◽  
Nervous System ◽  
Axon Guidance ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Guidance System ◽  
Laboratory Animals ◽  
Compelling Evidence ◽  
Deleted In Colorectal Cancer

Abstract Axon guidance molecules direct growing axons toward their targets, assembling the intricate wiring of the nervous system. One of these molecules, Netrin-1, and its receptor, DCC (deleted in colorectal cancer), has profound effects, in laboratory animals, on the adolescent expansion of mesocorticolimbic pathways, particularly dopamine. Now, a rapidly growing literature suggests that (1) these same alterations could occur in humans, and (2) genetic variants in Netrin-1 and DCC are associated with depression, schizophrenia, and substance use. Together, these findings provide compelling evidence that Netrin-1 and DCC influence mesocorticolimbic-related psychopathological states that emerge during adolescence.

Smad2 isoforms are differentially expressed during mouse brain development and aging

2009 ◽  
Vol 27 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Uwe Ueberham ◽  
Peggy Lange ◽  
Elke Ueberham ◽  
Martina K. Brückner ◽  
Maike Hartlage‐Rübsamen ◽  
...  
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Differentially Expressed ◽  
Development And Aging ◽  
Mouse Brain Development

scholarly journals Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Science ◽  
2018 ◽  
Vol 359 (6376) ◽  
pp. 693-697 ◽  
Author(s):  
Michael J. Gandal ◽  
Jillian R. Haney ◽  
Neelroop N. Parikshak ◽  
Virpi Leppa ◽  
Gokul Ramaswami ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Genetic Architecture ◽  
Brain Dysfunction ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Neuropsychiatric Disease ◽  
Transcriptional Dysregulation ◽  
Molecular Brain ◽  
Neuropsychiatric Illness

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, and alcoholism—compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism–based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.

scholarly journals A genome-wide association study of total child psychiatric problems scores

2020 ◽  
Author(s):  
Alexander Neumann ◽  
Ilja M. Nolte ◽  
Irene Pappa ◽  
Tarunveer S. Ahluwalia ◽  
Erik Pettersson ◽  
...  
Keyword(s):  
Association Study ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Psychiatric Problem ◽  
Problem Score ◽  
Genome Wide ◽  
A Genome ◽  
Psychiatric Problems

ABSTRACTSubstantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium. The SNP heritability of total psychiatric problems was 5.4% (SE=0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total psychiatric problem score were shared with known genetic variants for common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation of with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29).The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between psychiatric disorders and related traits.

scholarly journals Alpha‐ and beta‐tubulin isotypes are differentially expressed during brain development

2020 ◽  
Author(s):  
Torben J. Hausrat ◽  
Jennifer Radwitz ◽  
Franco L. Lombino ◽  
Petra Breiden ◽  
Matthias Kneussel
Keyword(s):  
Brain Development ◽  
Differentially Expressed ◽  
Beta Tubulin ◽  
Tubulin Isotypes
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