Large genetic map of psychiatric disorders completed

Last Updated on

March 15, 2020 –  An international study published in the journal Cell has described 109 genetic variants associated with eight psychiatric disorders such as autism, ADHD, schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder and Tourette syndrome in a total of about 230,000 patients worldwide.  A psychiatric disorder is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitting, or occur as a single episode. Signs and symptoms that vary widely between specific disorders

About 25% of the world population is affected by some type of psychiatric disease that can alter intellectual ability, behavior, affectivity and social relations. The present study, based on 230,000 affected patients and 500,000 control individuals, analyzes the genetic base shared by eight psychiatric pathologies and defines three groups of highly genetically related disorders. These three groups are a) diseases that respond to compulsive behaviors (anorexia nervosa (AN), obsessive-compulsive disorder), b) mood and psychotic disorders (bipolar disorder (BIP), major depression, and schizophrenia), and c) early-onset neurodevelopmental disorders (autism spectrum disorder (ASD), attention deficit hyperactivity disease (ADHD), and Tourette syndrome).

Those disorders listed in the same group tend to share more genetic risk factors between them than with other groups. Moreover, these groups built on the basis of genetic criteria match with the clinical output, i.e., disease phenotype.

This study did not, however, put emphasis on the genes shared by members of one of particular group of diseases above, but on the genes shared by the highest number of disorders. That is, it focused on those  genetic factors that would at the base of a predisposition for a  ‘sensitive’ brain, that would more likely suffer from any type of psychiatric disorder. And the fact that this could be one or another disorder would depend on specific genetic factors, not forgetting about the environmental factors. Many psychiatric disorders show comorbidities, i.e., they tend to co-occur, sometimes in a sequential manner. Therefore, it is quite likely for a patient to show more than one disorder throughout his/her lifetime.

According to the results, strangely as it may sound, the “Deleted in Colorectal Carcinoma” (DCC) gene, which also has a role und is related to the development of the nervous system, is a risk factor for all eight studied disorders. Also, the RNA binding protein, fox-1 homolog (RBFOX1) gene, which regulates the splicing in many genes, is involved in seven out of the eight disorders considered.

One of the most relevant findings of the study was that those genes that are risk factors for more than one disorder, i.e., genes with pleiotropic effects, are usually active during the second trimester of pregnancy, coinciding with a crucial stage in the development of the nervous system. Overall, the study suggest that genetic influences on psychiatric disorders comprise at least two general classes of genetic loci. The first comprises a set of genes that confer relatively broad liability to psychiatric disorders by acting on early neurodevelopment and the establishment of brain circuitry. These pleiotropic genes, on average, begin to come online by the second trimester of fetal development and exhibit differentially high expression thereafter. The expression and differentiation of this generalized genetic risk into discrete psychiatric syndromes (e.g., ASD, BIP, AN) may then involve direct and/or interactive effects of additional sets of common and rare loci and environmental factors, possibly mediated by epigenetic effects, that shape phenotypic expression via effects on brain structure/function and behavior.

Apart from genomics, the study focused on the analysis of functional aspects of the genetic risk variants such as the impact on gene expression in space (i.e., which organs, specific regions of the brain, tissues and even cells do express the disease genes) and in time (i.e., in what developmental phase of the individual genes are active). Moreover, the study revealed a seemingly odd behaviour in that some genetic variations can act as genetic risk factors in a certain disorder but they have a protecting effect in other cases. Thus, eleven areas of the genome in which the effects are opposed in different pairs of disorders, that is, protection in one case, and susceptibility in the other. This could make sense in some instances in which there would be a genetic variant with contrary effects in ADHD, a disorder usually related to obesity, and anorexia. However, regarding the neurodevelopmental disorders such as autism and schizophrenia, there are genetic variants with opposite effects and others that work in the same direction. In summary then, this observations suggest that the genetics of psychiatric disorders is more complex than thought and needs still some research in order to solve and understand this complex puzzle.

See here a short sequence on psychiatric disorders:

Print Friendly, PDF & Email

 

 

Tags: , , , , , , , , , , , , , ,
About the Author
Joseph Gut - thasso Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Your opinion

Comment

@peepso_user_1(thassodotcom) Aren't we all compulsive, to some degree?
3 months ago 3 months ago
@peepso_user_7542(Menlo-50) @peepso_user_1(Joseph Gut) We are. Particularly when following and correct obsessively and painstakingly every smallest detail....
@peepso_user_1(thassodotcom) @peepso_user_7542(Jo Gut) That's it. Then it becomes a disease.
3 months ago 3 months ago

thasso: conditions

thasso: newest tweets

thasso: recent comments

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • The protein that stands between us and autoimmunity July 2, 2020
    The immune system is supposed to protect from external microbial invaders, but sometimes it turns its efforts inward, potentially resulting in autoimmune diseases. In a new study, researchers from Osaka University have discovered how reversible modifications to DNA by certain proteins protect from autoimmune diseases, and conversely, how the absence of these proteins paves the […]
  • Concern following gene therapy adverse events July 2, 2020
    The Editor-in-Chief of Human Gene Therapy, the first journal devoted to the field of gene therapy, and one of the world's leading experts on gene therapy have co-authored a new editorial, Moving Forward After Two Deaths in a Gene Therapy Trial of Myotubular Myopathy, in response to the news of two deaths in a now-halted […]
  • How a mutation on the novel coronavirus has come to dominate the globe July 2, 2020
    Flashback to mid-March: the novel coronavirus had reached San Diego, California. Few people could get tested, and even less was known about how the virus mutated as it spread from person to person.
  • High-definition likelihood inference of genetic correlations across human complex traits July 2, 2020
    Evaluating the genetic correlations across our phenotypes is of essential importance for understanding disease etiology and other potential causality. A new method—published in the journal Nature Genetics—vastly improves estimates of genetic correlations using established resources from genome-wide association studies.
  • Research team develops technology to improve effectiveness of stem cells in regenerative medicine July 2, 2020
    Stem cells have been holding great promise for regenerative medicine for years. In the last decade, several studies have shown that this type of cell, which in Spanish is called "mother cell" because of its ability to give rise to a variety of different cell types, can be applied in regenerative medicine for diseases such […]
  • Towards lasers powerful enough to investigate a new kind of physics July 3, 2020
    In a paper that made the cover of the journal Applied Physics Letters, an international team of researchers has demonstrated an innovative technique for increasing the intensity of lasers. This approach, based on the compression of light pulses, would make it possible to reach a threshold intensity for a new type of physics that has […]
  • Does DNA in the water tell us how many fish are there? July 3, 2020
    Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.
  • Fluorine enables separation-free 'chiral chromatographic analysis' July 2, 2020
    Researchers from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences recently developed a new platform for rapid chiral analysis, producing chromatogram-like output without the need for separation.
  • Hot flushes and night sweats linked to 70% increase in cardiovascular disease July 2, 2020
    New research from The University of Queensland has found that women who have hot flushes and night sweats after menopause are 70 per cent more likely to have heart attacks, angina and strokes.
  • The protein that stands between us and autoimmunity July 2, 2020
    Researchers from Osaka University identified the epigenetic proteins Tet2 and Tet3 as key regulators of B cell function. They showed that these proteins suppress B cell function and conversely, that Tet2/Tet3 knockout mice develop a mild form of systemic lupus erythematosus due to hyperactivation of T cells. These findings could help develop a novel treatment […]
Top