Alterations observed in the interferon \u03b1 and \u03b2 signaling pathway in MDD patients are marginally influenced by cis-acting alleles

Chiara Magri,Alessandra Minelli,Chiara Sacco,Massimo Gennarelli,Edoardo Giacopuzzi,Luisella Bocchio-Chiavetto

doi:10.1038/s41598-020-80374-2

Abstract

Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. Pieces of evidence indicate that inflammation and immune activation may contribute to the onset of MDD playing a role in the pathogenetic mechanism. To date, it is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Both components were tested for association with MDD. Many genes belonging to the α/β interferon signaling pathway showed an association between MDD and EReX, only two between MDD and GReX. Also other MDD differentially expressed genes were more influenced by the EReX than by GReX. These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway.

Highlights

Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors
In order to clarify this issue, we dissected gene expression data of a large genomic/transcriptomic dataset on MDD (463 cases with MDD and 459 c ontrols11) in its two components: the Genetically Regulated eXpression component (GReX) and the Environmental Regulated eXpression component (EReX); both components were tested for association with MDD
Genes belonging to the IFN α/β signaling pathway showed a significant association with MDD when the Environmental Regulated Expression (EReX) component was considered, whereas only two genes (MX1 and IRF7) resulted to be associated with MDD when the GReX component was taken into account

Summary

Introduction

Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. It is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Other MDD differentially expressed genes were more influenced by the EReX than by GReX These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway. It is not known to which extent the association between MDD and inflammation is shaped by the genetic background, environmental factors and/or their interaction

Methods

Results

Conclusion