title: A molecular pathway analysis informs the genetic background at risk for schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a complex mental disorder marked by severely impaired thinking, delusional thoughts, hallucinations and poor emotional responsiveness. The biological mechanisms that lead to schizophrenia may be related to the genetic background of patients. Thus, a genetic perspective may help to unravel the molecular pathways disrupted in schizophrenia.
  
  
  METHODS
  In the present work, we used a molecular pathway analysis to identify the molecular pathways associated with schizophrenia. We collected data of genetic loci previously associated with schizophrenia, identified the genes located in those positions and created the metabolic pathways that are related to those genes' products. These pathways were tested for enrichment (a number of SNPs associated with the phenotype significantly higher than expected by chance) in a sample of schizophrenic patients and controls (4486 and 4477, respectively).
  
  
  RESULTS
  The molecular pathway that resulted from the identification of all the genes located in the loci previously found to be associated with schizophrenia was found to be enriched, as expected (permutated p(10(6))=9.9999e-06).We found 60 SNPs amongst 30 different genes with a strong association with schizophrenia. The genes are related to the pathways related to neurodevelopment, apoptosis, vesicle traffic, immune response and MAPK cascade.
  
  
  CONCLUSIONS
  The pathway related to the toll-like receptor family seemed to play a central role in the modulation/connection of various pathways whose disruption leads to schizophrenia. This pathway is related to the innate immune system, further stressing the role of immunological-related events in increasing the risk to schizophrenia.
authors.affiliation: Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.affiliation: Department of Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, Bologna, Italy; I.R.C.C.S. "San Giovanni di Dio", Fatebenefratelli, Brescia, Italy. Electronic address: antonio.drago@unibo.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Drago
authors.affiliation: Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Calabrò
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.affiliation: Department of Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D051193:Toll-Like Receptors
keywords: Pathway analysis; Schizophrenia; TLR; Toll-like receptors