IP: Dr. Javier Costas Costas

Resumen del proyecto: The neurodevelopmental continuum model proposes that the origin of various mental disorders may be related to fetal neurodevelopmental alterations, with a gradient from highest to lowest severity, that affects autism spectrum disorders, schizophrenia and affective disorders. This neurodevelopmental impairment may be partly due to genetic variation affecting the physiology of the placenta that may confer a transdiagnostic genetic risk for psychiatric disorders of neurodevelopmental origin. The main aim of the project is to find a genomic biomarker of neurodevelopmental impairment based on genes highly expressed in placenta and with differential expression in the fetal portion of placentas from complicated pregnancies, using a transdiagnostic approach. To this goal, a collection of DNA from affective disorders patients will be generated, to be jointly analyzed with the already available collections of schizophrenia, autism spectrum disorders, and controls. The samples will be genotyped using the Axiom Spain Biobank Array, specifically designed for analysis of common as well as rare variants from Spanish population. A list of highly expressed placental genes whose expression is modulated by biological stress will be created, as well as a list of variants within these genes whose effect on the studied disorders follow the neurodevelopmental gradient in large GWAS. Three main test will be performed: i) a gene set enrichment analysis on available GWAS summary statistics data from consortia, to estimate the relevance of the placental gene set in each disorder; ii) a test of the cumulative role of rare variants at this gene set in the different disorders versus controls using our genotyping data sets, to test for additional evidence of the role of the gene set; and iii) a polygenic risk score analysis based on this gene set to test the expected gradient in our genotyping data sets in order to confirm its validity as a genomic marker of early neurodevelopmental impairment.

Entidad financiadora: Instituto de Salud Carlos III (Ministerio de Ciancia, Innovación y Universidades)