Large genetic map of psychiatric disorders completed

The present study, probably the most ambitious and detailed study published so far on the genetics of psychiatric disorders, was promoted by the Psychiatric Genomics Consortium (PGC), the most ambitious international platform on genetics of psychiatric conditions, led by the expert in psychiatric J. W. Smoller, from Harvard University (United States).  In the study participated collaborators from the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), the Research Institute Sant Joan de Déu (IRSJD), the Rare Diseases Networking Biomedical Research Centre (CIBERER), the Vall d’Hebron Research Institute (VHIR) and the Mental Health Networking Biomedical Research Centre (CIBERSAM). Apart from listing potential genetic predisposition and resilience factors of pathologies, this study’s time was to determine the specific genes that the pathologies share, and to complete the genetic map of psychiatric 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.

See here a short sequence on psychiatric disorders: