Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

New discoveries in schizophrenia genetics reveal neurobiological pathways: A review of recent findings.

ABSTRACT: Schizophrenia research has undergone a recent transformation. By leveraging large sample sizes, genome-wide association studies of common genetic variants have approximately tripled the number of candidate genetic loci. Rare variant studies have identified copy number variants that are schizophrenia risk loci. Among these, the 3q29 microdeletion is now known to be the single largest schizophrenia risk factor. Next-generation sequencing studies are increasingly used for rare variant association testing, and have already facilitated identification of large effect alleles. Collectively, recent findings implicate voltage-gated calcium channel and cytoskeletal pathways in the pathogenesis of schizophrenia. Taken together, these results suggest the possibility of imminent breakthroughs in the molecular understanding of schizophrenia.

SUBMITTER: Kotlar AV

PROVIDER: S-EPMC4679408 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

New discoveries in schizophrenia genetics reveal neurobiological pathways: A review of recent findings.

Kotlar Alex V AV Mercer Kristina B KB Zwick Michael E ME Mulle Jennifer G JG

European journal of medical genetics 20151019 12

Schizophrenia research has undergone a recent transformation. By leveraging large sample sizes, genome-wide association studies of common genetic variants have approximately tripled the number of candidate genetic loci. Rare variant studies have identified copy number variants that are schizophrenia risk loci. Among these, the 3q29 microdeletion is now known to be the single largest schizophrenia risk factor. Next-generation sequencing studies are increasingly used for rare variant association t ...[more]

PMID: 26493318

Similar Datasets

Understanding the genetics and neurobiological pathways behind addiction (Review).

Project description:The hypothesis issued by modern medicine states that many diseases known to humans are genetically determined, influenced or not by environmental factors, which is applicable to most psychiatric disorders as well. This article focuses on two pending questions regarding addiction: Why do some individuals become addicted while others do not? along with Is it a learned behavior or is it genetically predefined? Recent data suggest that addiction is more than repeated exposure, it is the synchronicity between intrinsic factors (genotype, sex, age, preexisting addictive disorder, or other mental illness), extrinsic factors (childhood, level of education, socioeconomic status, social support, entourage, drug availability) and the nature of the addictive agent (pharmacokinetics, path of administration, psychoactive properties). The dopamine-mesolimbic motivation-reward-reinforcement cycle remains the most coherent physiological theory in addiction. While the common property of addictive substances is that they are dopamine-agonists, each class has individual mechanisms, pharmacokinetics and psychoactive potentials.

| S-EPMC8014976 | biostudies-literature

Recent discoveries in the genetics of melanoma and their therapeutic implications.

Project description:The incidence of cutaneous malignant melanoma, tumors arising from melanocytes, has increased markedly over the past few years in many countries. Although early melanoma is curable through surgical excision, the prognosis of advanced melanoma is very poor, this tumor being resistant to current therapies. Thus there is a need for new therapies to improve the treatment of advanced melanoma. This review provides an overview of recent discoveries in the genetics of melanoma which could offer new therapeutic opportunities.

| S-EPMC2682195 | biostudies-literature

Primary glomerulonephritis: A review of important recent discoveries.

Project description:The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect.

| S-EPMC4714100 | biostudies-literature

Recent advances in the genetics of schizophrenia.

Project description:The genetic etiology of schizophrenia, a common and debilitating psychiatric disorder, is supported by a wealth of data. Review of the current findings suggests that considerable progress has been made in recent years, with a number of chromosomal regions consistently implicated by linkage analysis. Three groups have shown linkage to 1q21-22 using similar models, with HLOD scores of 6.5, 3.2, and 2.4. Other replicated loci include 13q32 that has been implicated by two independent groups with significant HLOD scores (4.42) or NPL values (4.18), and 5pl4.1-13.1, 5q21-33, 8p2l-22, and 10p11-15, each of which have been reported as suggestive by at least three separate groups. Different studies have also replicated evidence for a modest number of candidate genes that were not ascertained through linkage. Of these, the greatest support exists for the DRD3 (3q13.3), HTR2A (13q14.2), and CHRNA7 (15q13-q14) genes. The refinement of phenotypes, the use of endophenotypes, reduction of heterogeneity, and extensive genetic mapping have all contributed to this progress. The rapid expansion of information from the human genome project will likely further accelerate this progress and assist in the discovery of susceptibility genes for schizophrenia. A greater understanding of disease mechanisms and the application of pharmacogenetics should also lead to improvements in therapeutic interventions.

| S-EPMC3169644 | biostudies-literature

Recent Advances in the Genetics of Schizophrenia.

Project description:The last decade brought tremendous progress in the field of schizophrenia genetics. As a result of extensive collaborations and multiple technological advances, we now recognize many types of genetic variants that increase the risk. These include large copy number variants, rare coding inherited and de nov? variants, and over 100 loci harboring common risk variants. While the type and contribution to the risk vary among genetic variants, there is concordance in the functions of genes they implicate, such as those whose RNA binds the fragile X-related protein FMRP and members of the activity-regulated cytoskeletal complex involved in learning and memory. Gene expression studies add important information on the biology of the disease and recapitulate the same functional gene groups. Studies of alternative phenotypes help us widen our understanding of the genetic architecture of mental function and dysfunction, how diseases overlap not only with each other but also with non-disease phenotypes. The challenge is to apply this new knowledge to prevention and treatment and help patients. The data generated so far and emerging technologies, including new methods in cell engineering, offer significant promise that in the next decade we will unlock the translational potential of these significant discoveries.

| S-EPMC6032037 | biostudies-literature

Recent findings on genetics of systemic autoimmune diseases.

Project description:Association studies of over 1 million SNPs capturing most of the human genome common variation became possible thanks to the information provided by the HapMap International project and the development of high-throughput genotyping technologies at accessible prices. Genome-wide scans analyzing thousands of individuals have now identified most if not all of the major genes involved in susceptibility for several systemic autoimmune diseases. In particular, results for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) are reviewed here. While most genes are shared between diseases, few seem to be unique reflecting that we still are long before knowing all genes, their interactions with other genes and the environment and their impact on biological functions.

| S-EPMC2997852 | biostudies-literature

Genetics of Schizophrenia: Overview of Methods, Findings and Limitations.

Project description:Genetics constitute a crucial risk factor to schizophrenia. In the last decade, molecular genetic research has produced novel findings, infusing optimism about discovering the biological roots of schizophrenia. However, the complexity of the object of inquiry makes it almost impossible for non-specialists in genetics (e.g., many clinicians and researchers) to get a proper understanding and appreciation of the genetic findings and their limitations. This study aims at facilitating such an understanding by providing a brief overview of some of the central methods and findings in schizophrenia genetics, from its historical origins to its current status, and also by addressing some limitations and challenges that confront this field of research. In short, the genetic architecture of schizophrenia has proven to be highly complex, heterogeneous and polygenic. The disease risk is constituted by numerous common genetic variants of only very small individual effect and by rare, highly penetrant genetic variants of larger effects. In spite of recent advances in molecular genetics, our knowledge of the etiopathogenesis of schizophrenia and the genotype-environment interactions remain limited.

| S-EPMC5480258 | biostudies-other

Genetics of schizophrenia (Review).

Project description:A comprehensive review of the body of genetic studies on schizophrenia seems even more daunting than the battle a psychiatrist wages daily in the office with her archenemy of a thousand faces. The following article reunites some genetic, epigenetic and environmental factors of schizophrenia from revered and vast studies in a chronological and progressive fashion. Twin studies set the basics of heritability and a particular study by Davis and Phelps considers the widely ignored influence of prenatal environment in the development of schizophrenia. Mostly ignited by linkage studies, candidate gene studies explore further by fine-mapping the hypothesized variants [mostly in the forms single nucleotide polymorphisms (SNPs) and less but with greater impact copy number variations (CNVs)] associated with the disease. Genome-wide association studies (GWAS) increase considerably the sample sizes and thus the validity of the results, while the next-generation sequencing (NGS) attain the highest yet unreplicated level of validity results.

| S-EPMC7465115 | biostudies-literature

Schizophrenia and genetics: new insights.

Project description:There is consistent evidence that the principal etiology of schizophrenia involves predisposing genetic factors. Recent years have seen several new insights in the genetics of schizophrenia. Several chromosomal regions show significant evidence that they contain schizophrenia susceptibility genes. A clinically relevant genetic subtype of schizophrenia (22q deletion syndrome) has been identified. There is new evidence that spontaneous mutations may play a role. There are new recommendations for genetic counseling. The progress to date suggests that understanding of a neurodevelopmental pathway from genetic susceptibility to schizophrenia will soon be fundamentally altered by molecular genetic advances in this complex disease.

| S-EPMC3188303 | biostudies-literature

Synovial sarcoma: recent discoveries as a roadmap to new avenues for therapy.

Project description:UnlabelledOncogenesis in synovial sarcoma is driven by the chromosomal translocation t(X,18; p11,q11), which generates an in-frame fusion of the SWI/SNF subunit SS18 to the C-terminal repression domains of SSX1 or SSX2. Proteomic studies have identified an integral role of SS18-SSX in the SWI/SNF complex, and provide new evidence for mistargeting of polycomb repression in synovial sarcoma. Two recent in vivo studies are highlighted, providing additional support for the importance of WNT signaling in synovial sarcoma: One used a conditional mouse model in which knockout of β-catenin prevents tumor formation, and the other used a small-molecule inhibitor of β-catenin in xenograft models.SignificanceSynovial sarcoma appears to arise from still poorly characterized immature mesenchymal progenitor cells through the action of its primary oncogenic driver, the SS18-SSX fusion gene, which encodes a multifaceted disruptor of epigenetic control. The effects of SS18-SSX on polycomb-mediated gene repression and SWI/SNF chromatin remodeling have recently come into focus and may offer new insights into the basic function of these processes. A central role for deregulation of WNT-β-catenin signaling in synovial sarcoma has also been strengthened by recent in vivo studies. These new insights into the the biology of synovial sarcoma are guiding novel preclinical and clinical studies in this aggressive cancer.

| S-EPMC4320664 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data