TY - JOUR
T1 - Enrichment pathway analysis. The inflammatory genetic background in Bipolar Disorder
AU - Drago, Antonio
AU - Crisafulli, Concetta
AU - Calabrò, Marco
AU - Serretti, Alessandro
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - INTRODUCTION: The pathophysiology of Bipolar Disorder (BD) is yet to be fully characterized. In the last years attention was focused on neurodevelopment or neurodegenerative events. In this context, hyper- and hypo- activation of inflammatory cascades may play a role in modulating the architecture and function of neuronal tissues. In the present paper we tested the enrichment of molecular pathways related to inflammatory cascades (IL-1, IL-2, IL-6, IL-8, TNF and INF) testing whether genes related to these systems hold more variations associated with the risk for BD than expected.METHODS: ~7000 bipolar patients and controls with genome-wide data available from NIMH dataset were analyzed. SNPs were imputed, checked for quality control, pruned and tested for association (0.01RESULTS: As a result, IL-6, IL-8 and IFN related pathways held twice to thrice the number of expected variants associated with BD. These tests resisted the permutation analysis.LIMITATIONS: The restricted number of inflammatory components included in the analysis and the lack of functional consequences for some of the SNPs analyzed may be biased; however, these choices helped the authors to lighten the statistical computational load for the analyses and at the same time included possibly hidden SNPs in linkage disequilibrium with the analyzed variations.CONCLUSIONS: We bring evidence that the inflammatory cascades may be genetically varied in Bipolar patients. This genetic background may explain part of the pathophysiology of the disorder.
AB - INTRODUCTION: The pathophysiology of Bipolar Disorder (BD) is yet to be fully characterized. In the last years attention was focused on neurodevelopment or neurodegenerative events. In this context, hyper- and hypo- activation of inflammatory cascades may play a role in modulating the architecture and function of neuronal tissues. In the present paper we tested the enrichment of molecular pathways related to inflammatory cascades (IL-1, IL-2, IL-6, IL-8, TNF and INF) testing whether genes related to these systems hold more variations associated with the risk for BD than expected.METHODS: ~7000 bipolar patients and controls with genome-wide data available from NIMH dataset were analyzed. SNPs were imputed, checked for quality control, pruned and tested for association (0.01RESULTS: As a result, IL-6, IL-8 and IFN related pathways held twice to thrice the number of expected variants associated with BD. These tests resisted the permutation analysis.LIMITATIONS: The restricted number of inflammatory components included in the analysis and the lack of functional consequences for some of the SNPs analyzed may be biased; however, these choices helped the authors to lighten the statistical computational load for the analyses and at the same time included possibly hidden SNPs in linkage disequilibrium with the analyzed variations.CONCLUSIONS: We bring evidence that the inflammatory cascades may be genetically varied in Bipolar patients. This genetic background may explain part of the pathophysiology of the disorder.
KW - Bipolar Disorder/genetics
KW - Case-Control Studies
KW - Databases, Genetic
KW - Female
KW - Genetic Background
KW - Genetic Predisposition to Disease/genetics
KW - Genome-Wide Association Study
KW - Humans
KW - Inflammation/genetics
KW - Inflammation Mediators
KW - Male
KW - Polymorphism, Single Nucleotide/genetics
KW - Signal Transduction/genetics
U2 - 10.1016/j.jad.2015.03.032
DO - 10.1016/j.jad.2015.03.032
M3 - Journal article
C2 - 25855618
SN - 0165-0327
VL - 179
SP - 88
EP - 94
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -