Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
A molecular pathway analysis informs the genetic background at risk for schizophrenia. / Crisafulli, Concetta; Drago, Antonio; Calabrò, Marco; Spina, Edoardo; Serretti, Alessandro.
I: Progress in Neuro-Psychopharmacology & Biological Psychiatry, Bind 59, 03.06.2015, s. 21-30.Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - A molecular pathway analysis informs the genetic background at risk for schizophrenia
AU - Crisafulli, Concetta
AU - Drago, Antonio
AU - Calabrò, Marco
AU - Spina, Edoardo
AU - Serretti, Alessandro
N1 - Copyright © 2014. Published by Elsevier Inc.
PY - 2015/6/3
Y1 - 2015/6/3
N2 - 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.
AB - 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.
KW - Databases, Factual
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Metabolic Networks and Pathways
KW - Polymorphism, Single Nucleotide
KW - Schizophrenia
KW - Signal Transduction
KW - Toll-Like Receptors
U2 - 10.1016/j.pnpbp.2014.12.009
DO - 10.1016/j.pnpbp.2014.12.009
M3 - Journal article
C2 - 25554435
VL - 59
SP - 21
EP - 30
JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry
SN - 0278-5846
ER -