Antonio Drago1, Concetta Crisafulli2, Marco Calabrò3, Alessandro Serretti4. 1. I.R.C.C.S. "San Giovanni di Dio", Fatebenefratelli, Brescia, Italy. Electronic address: antonio.drago76@gmail.com. 2. Department of Biomedical Science and morphological and functional images, University of Messina, Messina, Italy. 3. 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. 4. Department of Biomedical and Neuromotor Sciences - DIBINEM -, University of Bologna, Bologna, Italy.
Abstract
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 (0.01<p). Fisher test was conducted to test the enrichment within the pathways and the association was permutated (10(5) times) to limit false positive findings. RESULTS: 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.
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 bipolarpatients and controls with genome-wide data available from NIMH dataset were analyzed. SNPs were imputed, checked for quality control, pruned and tested for association (0.01<p). Fisher test was conducted to test the enrichment within the pathways and the association was permutated (10(5) times) to limit false positive findings. RESULTS: 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 Bipolarpatients. This genetic background may explain part of the pathophysiology of the disorder.
Authors: Philippe Leff-Gelman; Ismael Mancilla-Herrera; Mónica Flores-Ramos; Carlos Cruz-Fuentes; Juan Pablo Reyes-Grajeda; María Del Pilar García-Cuétara; Marielle Danitza Bugnot-Pérez; David Ellioth Pulido-Ascencio Journal: Neurosci Bull Date: 2016-07-18 Impact factor: 5.203
Authors: Annica J Rasmusson; Maike Gallwitz; Bardia Soltanabadi; Diana M Ciuculete; Jonas Mengel-From; Kaare Christensen; Marianne Nygaard; Mette Soerensen; Adrian E Boström; Robert Fredriksson; Eva Freyhult; Jessica Mwinyi; Darina Czamara; Elisabeth B Binder; Helgi B Schiöth; Janet L Cunningham Journal: Transl Psychiatry Date: 2021-06-24 Impact factor: 6.222